Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

To Compare the Effects of Immediate-release Tacrolimus and Astagraf XL on Donor-Specific Antibody (DSA) Formation and the Development of Immune Activation (IA) in de Novo Kidney Transplant Recipients (ASTOUND)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02723591
Recruitment Status : Completed
First Posted : March 30, 2016
Results First Posted : June 29, 2020
Last Update Posted : August 4, 2020
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Kidney Transplantation
Interventions Drug: Tacrolimus
Drug: Tacrolimus immediate release
Enrollment 599
Recruitment Details  
Pre-assignment Details Participants of ≥16 years and ≤70 of age requiring kidney transplant were enrolled. Randomization was stratified by alemtuzumab (yes/no), kidney donor profile index (KDPI) (3 levels: N/A [living donors] versus ≤50 versus >50), and human leukocyte antigens (HLA) Class II mismatch (yes/no).
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release Twice Daily (BID)
Hide Arm/Group Description Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 milligram per kilogram (mg/kg), once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 nanogram per milliliter (ng/mL) at all times during the study. Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Period Title: Overall Study
Started 300 299
Completed 204 198
Not Completed 96 101
Reason Not Completed
Adverse Event             48             40
Death             2             2
Lack of Efficacy             4             3
Lost to Follow-up             1             7
Protocol Violation             20             23
Withdrawal by Subject             4             8
Randomized but Never Received StudyDrug             12             12
Miscellaneous             5             6
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID Total
Hide Arm/Group Description Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study. Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study. Total of all reporting groups
Overall Number of Baseline Participants 300 299 599
Hide Baseline Analysis Population Description
The randomized set consisted of all participants who were randomized to receive the study drug (Astagraf XL or BID tacrolimus).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 300 participants 299 participants 599 participants
49  (11.7) 48.5  (11.6) 48.8  (11.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 300 participants 299 participants 599 participants
Female
111
  37.0%
91
  30.4%
202
  33.7%
Male
189
  63.0%
208
  69.6%
397
  66.3%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 300 participants 299 participants 599 participants
Hispanic or Latino
32
  10.7%
34
  11.4%
66
  11.0%
Not Hispanic or Latino
268
  89.3%
265
  88.6%
533
  89.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 300 participants 299 participants 599 participants
American Indian or Alaska Native
4
   1.3%
1
   0.3%
5
   0.8%
Asian
10
   3.3%
14
   4.7%
24
   4.0%
Native Hawaiian or Other Pacific Islander
2
   0.7%
1
   0.3%
3
   0.5%
Black or African American
58
  19.3%
67
  22.4%
125
  20.9%
White
212
  70.7%
200
  66.9%
412
  68.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
14
   4.7%
16
   5.4%
30
   5.0%
1.Primary Outcome
Title Percentage of Participants Who Were Positive for de Novo DSA (dnDSA) or Immune Activation (IA) Occurrence
Hide Description DSA was considered as a categorical (binary) variable with positivity determined at a threshold criteria approaching mean fluorescence intensity (MFI)=1000 at any time during the study. IA was considered either present or absent using the Trugraf™ v2.0 molecular assay. A negative designation (Trugraf TX Normal) was referred to as Immune Quiescence (IQ). Due to operating characteristics of the assay, a positive designation was considered evidence of IA in all participants.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The Modified Full Analysis Set (mFAS) consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
35.6 34.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments Logistic regression with DSA/IA occurrence by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant calculated panel reactivity antibody (cPRA) as fixed effects, and pooled site as a random effect with standard variance components covariance type.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5777
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.115
Confidence Interval (2-Sided) 95%
0.760 to 1.636
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Who Were Positive, Negative or Indeterminate for dnDSA Occurrence
Hide Description DSA was considered as a categorical (binary) variable with positivity determined at a threshold criteria approaching MFI=1000 at any time during the study. Indeterminate was defined as MFI signal was >1000 and DSA was suspected, but could not be confirmed due to inadequate donor typing. Participants whose samples for the test were not available were reported as unknown.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
Positive 5.5 4.3
Negative 90.5 92.8
Indeterminate 4 2.5
Unknown 0 0.4
3.Secondary Outcome
Title Peak Mean Fluorescence Intensity (MFI) of DSA Positive Participants
Hide Description Peak MFI of DSA positive participants was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. Only those mFAS participants who tested positive for dnDSA were included in the analyses.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 15 12
Median (Full Range)
Unit of Measure: fluorescence intensity unit
6119.21
(1320.0 to 29317.6)
2727.99
(1066.0 to 19971.5)
4.Secondary Outcome
Title Percentage of DSA Positive Participants With Weak, Moderate and Strong Antibody Strentgh
Hide Description DSA was considered as a categorical (binary) variable with positivity determined at a threshold criteria approaching MFI=1000 at any time during the study.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. Only those mFAS participants who tested positive for dnDSA were included in the analyses.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 15 12
Measure Type: Number
Unit of Measure: percentage of participants
Weak 0 0
Moderate 73.3 83.3
Strong 26.7 16.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from a 2x3 Exact Test of treatment by strength levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6618
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of DSA Positive Participants With DSA Persistence
Hide Description DSA was regarded as persistent under the following conditions: (i) DSA was detected and remained above the threshold for positivity (MFI = 1000) for two consecutive or nonconsecutive measurements, or (ii) the new appearance of a DSA at the threshold for positivity when preceded by a DSA of a different specificity that had subsequently become non-detectable.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. Only those mFAS participants who tested positive for dnDSA were included in the analyses.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 15 12
Measure Type: Number
Unit of Measure: percentage of participants
73.3 50
6.Secondary Outcome
Title Percentage of Participants Who Were Positive or Negative for Complement Component 1, Q Subcomponent (C1q)-Binding DSA
Hide Description Percentage of participants who were positive or negative for C1q-binding DSA were reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
Positive 1.8 0.4
Negative 98.2 99.6
7.Secondary Outcome
Title Percentage of Participants Who Were Positive or Negative for DSA Immunoglobulin G (IgG3) Isotype
Hide Description Percentage of participants who were positive or negative for IgG3 isotype were reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
Positive 0.7 1.1
Negative 99.3 98.9
8.Secondary Outcome
Title Percentage of DSA Positive Participants With Human Leukocyte Antigen, Class II, DQ Locus (HLA-DQ)
Hide Description Percentage of DSA positive participants with HLA-DQ Class-II were reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. Only those mFAS participants who tested positive for DSA were included in the analyses.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 15 12
Measure Type: Number
Unit of Measure: percentage of participants
40 25
9.Secondary Outcome
Title Percentage of Participants Who Were Positive for IA Occurrence From Day 1 to Day 365 Visit
Hide Description IA was considered either present or absent using the Trugraf™ v2.0 molecular assay. A negative designation (Trugraf TX Normal) was referred to as Immune Quiescence (IQ). Due to operating characteristics of the assay, a positive designation was considered evidence of IA in all participants.
Time Frame From day 1 to day 365 visit
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
31.3 31.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments Logistic regression with IA occurrence by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant cPRA as fixed effects, and pooled site as a random effect with standard Variance Components covariance type.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8518
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.038
Confidence Interval (2-Sided) 95%
0.700 to 1.539
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants Who Were Positive for IA Occurrence From Day 30 to Day 365 Visit
Hide Description IA was considered either present or absent using the Trugraf™ v2.0 molecular assay. A negative designation (Trugraf TX Normal) was referred to as Immune Quiescence (IQ). Due to operating characteristics of the assay, a positive designation was considered evidence of IA in all participants.
Time Frame From day 30 to day 365 visit
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
21.8 21.9
11.Secondary Outcome
Title Percentage of Participants With IA Persistence
Hide Description IA was regarded as persistent under the following conditions: (i) IA was detected and remained above the threshold for positivity for two consecutive or non-consecutive measurements, or (ii) the new appearance of an IA at the threshold for positivity when preceded by an IA of a different specificity that had subsequently become non-detectable.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
7.3 10
12.Secondary Outcome
Title Percentage of Participants With Presence of Transplant Glomerulopathy (TG) on Biopsy
Hide Description TG was defined as chronic glomerulopathy (cg) >0 on centrally-interpreted institutional protocol biopsy or biopsy obtained for cause during the first year post-transplant with +2 months visit window.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The Biopsy Analysis Dataset (BAS) consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
6.5 6.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from a 2-sided Fisher's Exact Test of treatment arm by response.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
13.Secondary Outcome
Title Percentage of Participants With Presence of Microcirculatory Inflammation (MI) on Biopsy
Hide Description MI was defined as glomerulitis (g) + peritubular capillaritis (ptc)>=2 on centrally-interpreted institutional protocol biopsy or biopsy obtained for cause during the first year post-transplant, with +2 months visit window.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
8.9 5.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from a 2-sided Fisher's Exact Test of treatment arm by response.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4750
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants With Presence of Interstitial Fibrosis and Tubular Atrophy (IFTA) and Inflammation on Biopsy
Hide Description IFTA and inflammation was defined as IFTA positive and inflammation positive (i >0) on centrally-interpreted institutional protocol biopsy or biopsy obtained for cause during the first year posttransplant, with +2 months visit window.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
26 16.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from a 2-sided Fisher's Exact Test of treatment arm by response.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0939
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
15.Secondary Outcome
Title Percentage of Participants With Estimated Glomerular Filtration Rate (eGFR) Threshold of <30 Millimetre Per Minute Per 1.73 Meter Square (mL/Min/1.73m^2)
Hide Description The eGFR was calculated using the Modification of Diet in Renal Disease (MDRD) formula.
Time Frame At 1 year post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
1.5 1.8
16.Secondary Outcome
Title Percentage of Participants With eGFR Threshold of <40 mL/Min/1.73m^2
Hide Description The eGFR was calculated using the MDRD formula.
Time Frame At 1 year post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
9.5 5.7
17.Secondary Outcome
Title Percentage of Participants With eGFR Threshold of <50 mL/Min/1.73m^2
Hide Description The eGFR was calculated using the MDRD formula.
Time Frame At 1 year post transplant
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
25.5 19.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments Logistic regression with occurrence of eGFR < 50 by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant cPRA as fixed effects, and pooled site as a random effect with standard Variance Components covariance type.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1160
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.431
Confidence Interval (2-Sided) 95%
0.915 to 2.240
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Percentage of Participants With a Five-point Decline in eGFR
Hide Description The eGFR was calculated using the MDRD formula.
Time Frame From 30 days post transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
13.1 11.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments Logistic regression with occurrence of 5-point eGFR decline by Month 12 as response, with treatment group, planned Campath use, KDPI level (as recorded in IVRS), HLA Class II mismatch, recipient age, recipient gender, recipient race, and pre-transplant cPRA as fixed effects, and pooled site as a random effect with standard Variance Components covariance type.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4995
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.212
Confidence Interval (2-Sided) 95%
0.693 to 2.120
Estimation Comments [Not Specified]
19.Secondary Outcome
Title eGFR at Day 30, Day 90, Day 180, Day 270 and Day 365
Hide Description The eGFR was calculated using the MDRD formula.
Time Frame Day 30, day 90, day 180, day 270 and day 365
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study. mFAS population with available data at each time point.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 265 271
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73 m^2
Day 30 Number Analyzed 265 participants 271 participants
50.86  (17.27) 52.72  (19.40)
Day 90 Number Analyzed 250 participants 252 participants
55.56  (16.00) 57.10  (19.99)
Day 180 Number Analyzed 230 participants 229 participants
56.81  (15.84) 58.33  (17.51)
Day 270 Number Analyzed 215 participants 212 participants
57.19  (16.84) 59.04  (18.19)
Day 365 Number Analyzed 204 participants 193 participants
58.25  (16.51) 60.94  (17.83)
20.Secondary Outcome
Title Percentage of Participants With Graft Loss
Hide Description Graft loss was defined as re-transplantation, transplant nephrectomy, or a return to dialysis for at least a six week duration, or participants' death.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
1.5 1.4
21.Secondary Outcome
Title Percentage of Participants Who Died
Hide Description Percentage of participants who died were reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
0.7 0.7
22.Secondary Outcome
Title Percentage of Participants With Biopsy-Proven Acute Rejection (BPAR)
Hide Description Positivity was determined by local biopsy, central pathology, or reported adverse events.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
7.6 8.2
23.Secondary Outcome
Title Percentage of Participants Who Were Lost to Follow-up
Hide Description Percentage of participants who were lost to follow-up were reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
0 0.7
24.Secondary Outcome
Title Percentage of Participants With Either Graft Loss, Death, BPAR or Lost to Follow-up
Hide Description Percentage of participants with either graft loss, death, BPAR or lost to follow-up were reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
9.1 10.4
25.Secondary Outcome
Title Percentage of Participants With Any Antibody-Mediated Rejection (ABMR)
Hide Description Percentage of participants with ABMR were reported. Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. A positive assessment is defined as antibody mediated changes that are diagnosed as either acute ABMR or chronic active ABMR.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Measure Type: Number
Unit of Measure: percentage of participants
1.6 0.7
26.Secondary Outcome
Title Percentage of Participants With Normal Biopsy Findings
Hide Description Percentage of participants with normal biopsy findings were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
6.5 4.4
27.Secondary Outcome
Title Percentage of Participants With C4d Deposition Without Active Rejection
Hide Description Percentage of participants with C4d deposition without active rejection were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 posttransplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
0.8 0.7
28.Secondary Outcome
Title Percentage of Participants With Acute ABMR
Hide Description Percentage of participants with acute ABMR were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 posttransplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
1.6 0.7
29.Secondary Outcome
Title Percentage of Participants With Grade I, II and III Acute ABMR
Hide Description Percentage of participants with grade I, II and III acute ABMR were reported. Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Acute ABMR was graded as Grade I: acute tubular necrosis-like -like minimal inflammation, Grade II: Capillary and or glomerular inflammation (ptc/g >0) and/or thromboses, and Grade III: arterial - v3.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment. Only those BAS participants who had acute AMBR were included in the analyses.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 2 1
Measure Type: Number
Unit of Measure: percentage of participants
Grade I 50 0
Grade II 50 100
Grade III 0 0
30.Secondary Outcome
Title Percentage of Participants With Chronic ABMR
Hide Description Percentage of participants with chronic ABMR were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
0 0
31.Secondary Outcome
Title Percentage of Participants With Borderline Changes
Hide Description Percentage of participants with borderline changes were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
14.6 14.7
32.Secondary Outcome
Title Percentage of Participants With Acute T-cell Mediated Rejection (TCMR)
Hide Description Percentage of participants with acute TCMR were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
6.5 5.9
33.Secondary Outcome
Title Percentage of Participants With Chronic TCMR
Hide Description Percentage of participants with chronic TCMR were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment. Only those BAS participants who had TCMR were included in the analyses.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 8 8
Measure Type: Number
Unit of Measure: percentage of participants
25 12.5
34.Secondary Outcome
Title Percentage of Participants With Grade I, II and III IFTA
Hide Description Percentage of participants with Grade I, II and III IFTA were reported. Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. IFTA was graded as Grade I: mild interstitial fibrosis and tubular atrophy (<25% of cortical area), Grade II: moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area), and Grade III: severe interstitial fibrosis and tubular atrophy/ loss (>50% of cortical area).
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Grade I 54.5 56.6
Grade II 18.7 15.4
Grade III 5.7 6.6
35.Secondary Outcome
Title Percentage of Participants With Any Additional Findings
Hide Description Percentage of participants with any additional findings (other than Normal biopsy, borderline changes, acute and chronic ABMR, Grade I, II, and III ABMR, C4D deposition, acute and chronic TCMR, Grade I, II, and III TCMR, Grade I, II and III IFTA, acute tubular necrosis, interstitial nephritis, pyelonephritis, bk virus, calcineurin inhibitor toxicity, hemolytic uremic syndrome and recurrent disease) were reported.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
29.3 34.6
36.Secondary Outcome
Title Percentage of Participants With Glomerulitis (g) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No glomerulitis, Score 1= <25% glomerulitis, Score 2= 25 to 75% glomerulitis and Score 3= >75% glomerulitis.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 89.4 90.4
Banff Lesion Score 1 5.7 6.6
Banff Lesion Score 2 4.1 1.5
Banff Lesion Score 3 0 0
Not able to score 0.8 1.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6327
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
37.Secondary Outcome
Title Percentage of Participants With Tubulitis (t) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No mononuclear cells in tubules or single focus of tubulitis only, Score 1= Foci with 1 to 4 mononuclear cells/tubular cross section (or 10 tubular cells), Score 2= Foci with 5 to 10 mononuclear cells/tubular cross section (or 10 tubular cells) and Score 3= Foci with >10 mononuclear cells/tubular cross section or the presence of ≥2 areas of tubular basement membrane destruction accompanied by i2/i3 inflammation and t2 elsewhere.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 79.7 79.4
Banff Lesion Score 1 16.3 15.4
Banff Lesion Score 2 1.6 1.5
Banff Lesion Score 3 1.6 2.9
Not able to score 0.8 0.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9701
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
38.Secondary Outcome
Title Percentage of Participants With Intimal Arteritis (v) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No arteritis, Score 1= Mild to moderate intimal arteritis in at least 1 arterial cross section, Score 2= Severe intimal arteritis with at least 25% luminal area lost in at least 1 arterial cross section and Score 3= Transmural arteritis and/or arterial fibrinoid change and medial smooth muscle necrosis with lymphocytic infiltrate in vessel.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: Percentage of Participants
Banff Lesion Score 0 93.5 94.9
Banff Lesion Score 1 2.4 2.2
Banff Lesion Score 2 2.4 0
Banff Lesion Score 3 0 0
Not able to score 1.6 2.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3127
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
39.Secondary Outcome
Title Percentage of Participants With Mononuclear Cell Interstitial Inflammation (i) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No inflammation or in less than 10% of unscarred cortical parenchyma, Score 1= Inflammation in 10 to 25% of unscarred cortical parenchyma, Score 2= Inflammation in 26 to 50% of unscarred cortical parenchyma and Score 3= Inflammation in more than 50% of unscarred cortical parenchyma.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 68.3 76.5
Banff Lesion Score 1 26.8 17.6
Banff Lesion Score 2 4.1 2.2
Banff Lesion Score 3 0 2.9
Not able to score 0.8 0.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0830
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
40.Secondary Outcome
Title Percentage of Participants With Glomerular Basement Membrane Double Contours (cg) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No GBM double contours by light microscopy (LM) or electron microscopy (EM), Score 1= No GBM double contours by LM but GBM double contours (incomplete or circumferential) in at least 3 glomerular capillaries by EM or Double contours of the GBM in 1-25% of capillary loops in the most affected nonsclerotic glomerulus by LM , Score 2= Double contours affecting 26 to 50% of peripheral capillary loops in the most affected-glomerulus and Score 3= Double contours affecting more than 50% of peripheral capillary loops in the most affected-glomerulus.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 93.5 93.4
Banff Lesion Score 1 5.7 3.7
Banff Lesion Score 2 0 1.5
Banff Lesion Score 3 0 0
Not able to score 0.8 1.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6022
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
41.Secondary Outcome
Title Percentage of Participants With Tubular Atrophy (ct) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No tubular atrophy, Score 1= Tubular atrophy involving up to 25% of the area of cortical tubules, Score 2= Tubular atrophy involving 26 to 50% of the area of cortical tubules and Score 3= Tubular atrophy involving in >50% of the area of cortical tubules.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 20.3 21.3
Banff Lesion Score 1 53.7 55.9
Banff Lesion Score 2 19.5 15.4
Banff Lesion Score 3 5.7 6.6
Not able to score 0.8 0.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments [Not Specified]
Type of Statistical Test Superiority
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Statistical Test of Hypothesis P-Value 0.9249
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
42.Secondary Outcome
Title Percentage of Participants With Interstitial Fibrosis (ci) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= Interstitial fibrosis in up to 5% of cortical area, Score 1= Interstitial fibrosis in 6 to 25%of cortical area (mild interstitial fibrosis), Score 2= Interstitial fibrosis in 26 to 50% of cortical area (moderate interstitial fibrosis) and Score 3= Interstitial fibrosis in >50% of cortical area (severe interstitial fibrosis).
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 21.1 20.6
Banff Lesion Score 1 52.8 56.6
Banff Lesion Score 2 19.5 15.4
Banff Lesion Score 3 5.7 6.6
Not able to score 0.8 0.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9136
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
43.Secondary Outcome
Title Percentage of Participants With Vascular Fibrous Intimal Thickening (cv) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No chronic vascular changes, Score 1= Vascular narrowing of up to 25% luminal area by fibrointimal thickening, Score 2= Vascular narrowing of 26 to 50% luminal area by fibrointimal thickening and Score 3= Vascular narrowing of more than 50% luminal area by fibrointimal thickening.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had atleast 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 33.3 36
Banff Lesion Score 1 40.7 41.2
Banff Lesion Score 2 22 17.6
Banff Lesion Score 3 2.4 2.2
Not able to score 1.6 2.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8789
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
44.Secondary Outcome
Title Percentage of Participants With Arteriolar Hyalinosis (ah) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No periodic acid-Schiff (PAS)-positive hyaline arteriolar thickening, Score 1= Mild to moderate PAS-positive hyaline thickening in at least 1 arteriole, Score 2= Moderate to severe PAS-positive hyaline thickening in more than 1 arteriole and Score 3= Severe PAS-positive hyaline thickening in many arterioles.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 91.1 86.8
Banff Lesion Score 1 4.1 5.9
Banff Lesion Score 2 4.1 3.7
Banff Lesion Score 3 0 2.2
Not able to score 0.8 1.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5574
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
45.Secondary Outcome
Title Percentage of Participants With Peritubular Capillaritis (Ptc) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= Maximum number of leukocytes <3, Score 1= At least 1 leukocyte cell in ≥10% of cortical PTCs with 3-4 leukocytes in most severely involved PTC, Score 2= At least 1 leukocyte in ≥10% of cortical PTC with 5-10 leukocytes in most severely involved PTC and Score 3= At least 1 leukocyte in ≥10% of cortical PTC with >10 leukocytes in most severely involved PTC.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 91.1 90.4
Banff Lesion Score 1 3.3 5.1
Banff Lesion Score 2 4.9 2.9
Banff Lesion Score 3 0 0.7
Not able to score 0.8 0.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8150
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
46.Secondary Outcome
Title Percentage of Participants With Mesangial Matrix Expansion (mm) Biopsy Score Assessed Using Banff Lesion Scores
Hide Description Central pathology reading was performed as per the 2007 Update to the Banff '97 classification. Banff Lesion Scores assess the presence and the degree of histopathological changes in the different compartments of renal transplant biopsies, focusing primarily but not exclusively on the diagnostic features seen in rejection. [Roufosse C et. al 2018]. Here, Score 0= No more than mild mesangial matrix increase in any glomerulus, Score 1= At least moderate mesangial matrix increase in up to 25% of nonsclerotic glomeruli, Score 2= At least moderate mesangial matrix increase in 26% to 50% of nonsclerotic glomeruli and Score 3= At least moderate mesangial matrix increase in >50% of nonsclerotic glomeruli.
Time Frame From date of transplant until month 14
Hide Outcome Measure Data
Hide Analysis Population Description
The BAS consisted of all mFAS participants who had at least 1 post-transplant central pathology assessment.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 123 136
Measure Type: Number
Unit of Measure: percentage of participants
Banff Lesion Score 0 87.8 91.2
Banff Lesion Score 1 8.9 6.6
Banff Lesion Score 2 2.4 0.7
Banff Lesion Score 3 0 0
Not able to score 0.8 1.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tacrolimus, Extended Release (Astagraf XL®) Once Daily, Tacrolimus, Immediate Release BID
Comments P-values obtained from the Exact Test of treatment arm by Banff scoring levels.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5673
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
47.Secondary Outcome
Title Time to First Occurrence of DSA
Hide Description DSA was considered as a categorical (binary) variable with positivity determined at a threshold criteria approaching MFI=1000 at any time during the study.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
48.Secondary Outcome
Title Time to First Occurrence of HLA-DQ DSA
Hide Description Time to first occurrence of HLA-DQ DSA was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
49.Secondary Outcome
Title Time to First Occurrence of C1q-binding DSA
Hide Description Time to first occurrence of C1q-binding DSA was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
50.Secondary Outcome
Title Time to First Occurrence of DSA IgG3 Isotype
Hide Description Time to first occurrence of DSA IgG3 isotype was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
51.Secondary Outcome
Title Time to First Occurrence of IA
Hide Description Time to first occurrence of IA was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
52.Secondary Outcome
Title Time to First Occurrence of TG on Biopsy
Hide Description Time to first occurrence of TG on biopsy was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
53.Secondary Outcome
Title Time to Occurrence of Death
Hide Description Time to occurrence of death was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Median (95% Confidence Interval)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
No data is reported since median and confidence interval was not estimable (that is, not reached) in either treatment group due to low number of events.
54.Secondary Outcome
Title Time to First Occurrence of Local BPAR
Hide Description Time to first occurrence of local BPAR was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
55.Secondary Outcome
Title Time to First Occurrence of Acute Forms of ABMR
Hide Description Time to first occurrence of acute forms of ABMR was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
56.Secondary Outcome
Title Time to First Occurrence of Chronic Forms of ABMR
Hide Description Time to first occurrence of chronic forms of ABMR was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
57.Secondary Outcome
Title Time to First Occurrence of Acute TCMR
Hide Description Time to first occurrence of acute TCMR was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
58.Secondary Outcome
Title Time to First Occurrence of Chronic TCMR
Hide Description Time to first occurrence of chronic TCMR was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
59.Secondary Outcome
Title Time to First Occurrence of Borderline Changes
Hide Description Time to first occurrence of borderline changes was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
60.Secondary Outcome
Title Time to First Occurrence of IFTA
Hide Description Time to first occurrence of IFTA was reported.
Time Frame From date of transplant until 1 year
Hide Outcome Measure Data
Hide Analysis Population Description
The mFAS consisted of all participants who were randomized and who received at least 1 dose of study drug (Astagraf XL or BID tacrolimus), and whose pretransplant cross-matched antibody samples did not demonstrate preformed DSA for the duration of the study.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 275 279
Mean (Standard Deviation)
Unit of Measure: days
NA [1]   (NA) NA [1]   (NA)
[1]
Analysis of data was not performed because it was not possible to define the exact date of occurrence since the data only recorded the date of sample collection which could not be interpreted as the date of first occurrence.
61.Secondary Outcome
Title Percentage of Participants With Treatment-emergent Adverse Event(TEAEs), Related TEAEs, Treatment-emergent Serious Adverse Event (TESAEs), Related TESAEs, TEAEs Leading to Discontinuation of Study Treatment and TEAEs Leading to Death
Hide Description A TEAE was defined as an Adverse Event (AE) observed on or after the day of starting the administration of the test drug/comparative drug.
Time Frame From first dose of study drug up to 7 days after last dose of study drug (up to 2 years)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set (SAF) consisted of all participants who enrolled into the study and took at least 1 dose of study medication and was used for all safety, tolerability, and medication compliance related variables.
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description:
Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
Overall Number of Participants Analyzed 288 287
Measure Type: Number
Unit of Measure: percentage of participants
TEAEs 99.7 98.6
TEAEs related to study treatment 77.8 70.7
TESAEs 56.6 47.4
TESAEs related to study treatment 27.4 23.7
TEAEs causing discontinuation of study treatment 16.3 13.9
TEAEs leading to death 0.7 0.7
Time Frame From first dose of study drug up to 7 days after last dose of study drug (up to 2 years)
Adverse Event Reporting Description The SAF consisted of all participants who enrolled into the study and took at least 1 dose of study medication and was used for all safety, tolerability, and medication compliance related variables.
 
Arm/Group Title Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Hide Arm/Group Description Participants received tacrolimus extended release capsule (Astagraf XL) at a starting dose of 0.15 mg/kg, once daily, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study. Participants received tacrolimus immediate release capsule as per the institutionally-derived protocol, BID, orally within 48 hours of transplantation (per the treating physician's discretion) for up to 1 year. Dose adjustments were allowed such that participants receiving tacrolimus maintained a minimal trough concentration of 6 ng/mL at all times during the study.
All-Cause Mortality
Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Affected / at Risk (%) Affected / at Risk (%)
Total   2/288 (0.69%)      2/287 (0.70%)    
Hide Serious Adverse Events
Tacrolimus, Extended Release (Astagraf XL®) Once Daily Tacrolimus, Immediate Release BID
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   163/288 (56.60%)      136/287 (47.39%)    
Blood and lymphatic system disorders     
Anaemia  1  2/288 (0.69%)  2 6/287 (2.09%)  6
Febrile neutropenia  1  2/288 (0.69%)  2 3/287 (1.05%)  4
Haemorrhagic anaemia  1  2/288 (0.69%)  2 1/287 (0.35%)  1
Leukocytosis  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Leukopenia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Methaemoglobinaemia  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Neutropenia  1  5/288 (1.74%)  7 2/287 (0.70%)  2
Thrombotic microangiopathy  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Cardiac disorders     
Acute myocardial infarction  1  3/288 (1.04%)  3 2/287 (0.70%)  3
Angina pectoris  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Aortic valve stenosis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Atrial fibrillation  1  3/288 (1.04%)  3 2/287 (0.70%)  2
Bradycardia  1  3/288 (1.04%)  3 0/287 (0.00%)  0
Cardiac arrest  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Cardio-respiratory arrest  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Coronary artery disease  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Left ventricular failure  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Pericardial effusion  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Pulseless electrical activity  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Supraventricular extrasystoles  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Tachycardia  1  1/288 (0.35%)  1 2/287 (0.70%)  2
Congenital, familial and genetic disorders     
Congenital cystic kidney disease  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Ear and labyrinth disorders     
Vertigo positional  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Endocrine disorders     
Hyperparathyroidism  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hyperparathyroidism tertiary  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Gastrointestinal disorders     
Abdominal distension  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Abdominal hernia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Abdominal pain  1  2/288 (0.69%)  2 6/287 (2.09%)  10
Abdominal pain lower  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Abdominal pain upper  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Colitis  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Constipation  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Diabetic gastroparesis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Diarrhoea  1  7/288 (2.43%)  7 11/287 (3.83%)  11
Gastrointestinal haemorrhage  1  2/288 (0.69%)  2 1/287 (0.35%)  1
Gastrointestinal necrosis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Hiatus hernia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Ileus  1  0/288 (0.00%)  0 4/287 (1.39%)  4
Impaired gastric emptying  1  2/288 (0.69%)  5 0/287 (0.00%)  0
Intestinal obstruction  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Intra-abdominal fluid collection  1  2/288 (0.69%)  2 3/287 (1.05%)  3
Large intestine perforation  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Melaena  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Nausea  1  4/288 (1.39%)  6 5/287 (1.74%)  6
Obstructive pancreatitis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Odynophagia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Pancreatitis  1  3/288 (1.04%)  3 0/287 (0.00%)  0
Pancreatitis acute  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Rectal haemorrhage  1  1/288 (0.35%)  2 0/287 (0.00%)  0
Retroperitoneal haematoma  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Retroperitoneal haemorrhage  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Small intestinal obstruction  1  1/288 (0.35%)  1 1/287 (0.35%)  2
Vomiting  1  4/288 (1.39%)  7 7/287 (2.44%)  10
General disorders     
Asthenia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Chest pain  1  2/288 (0.69%)  2 5/287 (1.74%)  5
Death  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Fatigue  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Haemorrhagic cyst  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Implant site extravasation  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Incarcerated hernia  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Malaise  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Oedema peripheral  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Peripheral swelling  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Pyrexia  1  9/288 (3.13%)  10 8/287 (2.79%)  11
Hepatobiliary disorders     
Biliary tract disorder  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Gallbladder necrosis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Hepatitis acute  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hepatitis alcoholic  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Immune system disorders     
Anaphylactic reaction  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Kidney transplant rejection  1  12/288 (4.17%)  13 14/287 (4.88%)  17
Renal transplant failure  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Transplant rejection  1  2/288 (0.69%)  2 2/287 (0.70%)  2
Infections and infestations     
Abdominal abscess  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Abscess neck  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Anal abscess  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Arteriovenous fistula site infection  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Bacteraemia  1  4/288 (1.39%)  4 4/287 (1.39%)  4
Bronchitis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Cellulitis  1  4/288 (1.39%)  6 4/287 (1.39%)  6
Clostridium difficile colitis  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Clostridium difficile infection  1  2/288 (0.69%)  2 6/287 (2.09%)  6
Coccidioidomycosis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Cystitis  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Cytomegalovirus colitis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Cytomegalovirus infection  1  3/288 (1.04%)  3 2/287 (0.70%)  2
Cytomegalovirus viraemia  1  4/288 (1.39%)  4 6/287 (2.09%)  6
Diabetic foot infection  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Disseminated cytomegaloviral infection  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Enterobacter bacteraemia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Enterococcal bacteraemia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Enterococcal sepsis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Enterovirus infection  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Escherichia bacteraemia  1  0/288 (0.00%)  0 1/287 (0.35%)  2
Escherichia infection  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Escherichia urinary tract infection  1  3/288 (1.04%)  4 2/287 (0.70%)  3
Fungaemia  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Fungal oesophagitis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Gangrene  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Gastroenteritis  1  3/288 (1.04%)  3 3/287 (1.05%)  3
Gastroenteritis norovirus  1  2/288 (0.69%)  2 2/287 (0.70%)  2
Gastroenteritis viral  1  4/288 (1.39%)  4 1/287 (0.35%)  1
Incision site abscess  1  0/288 (0.00%)  0 2/287 (0.70%)  3
Infected cyst  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Infection in an immunocompromised host  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Influenza  1  2/288 (0.69%)  2 1/287 (0.35%)  1
Klebsiella bacteraemia  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Localised infection  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Lower respiratory tract infection bacterial  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Lymph node tuberculosis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Necrotising soft tissue infection  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Osteomyelitis  1  3/288 (1.04%)  4 2/287 (0.70%)  2
Paronychia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Perirectal abscess  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Peritonitis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Peritonitis bacterial  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Pneumonia  1  10/288 (3.47%)  11 7/287 (2.44%)  8
Pneumonia klebsiella  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Pneumonia legionella  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Pneumonia pseudomonal  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Polyomavirus-associated nephropathy  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Pseudomonal bacteraemia  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Pyelonephritis  1  1/288 (0.35%)  1 2/287 (0.70%)  2
Pyelonephritis acute  1  1/288 (0.35%)  1 2/287 (0.70%)  2
Rhinovirus infection  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Sepsis  1  7/288 (2.43%)  7 10/287 (3.48%)  10
Septic shock  1  1/288 (0.35%)  1 2/287 (0.70%)  2
Skin infection  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Staphylococcal bacteraemia  1  0/288 (0.00%)  0 3/287 (1.05%)  4
Staphylococcal infection  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Streptococcal urinary tract infection  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Subcutaneous abscess  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Tooth infection  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Upper respiratory tract infection  1  1/288 (0.35%)  1 2/287 (0.70%)  2
Urinary tract infection  1  16/288 (5.56%)  17 11/287 (3.83%)  12
Urinary tract infection bacterial  1  2/288 (0.69%)  2 2/287 (0.70%)  2
Urinary tract infection enterococcal  1  2/288 (0.69%)  2 2/287 (0.70%)  2
Urosepsis  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Viral infection  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Viral pharyngitis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Vulval abscess  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Vulval cellulitis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Wound infection  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Wound infection staphylococcal  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Injury, poisoning and procedural complications     
Abdominal wound dehiscence  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Animal bite  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Ankle fracture  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Complications of transplanted kidney  1  1/288 (0.35%)  1 2/287 (0.70%)  2
Delayed graft function  1  5/288 (1.74%)  5 4/287 (1.39%)  4
Fall  1  2/288 (0.69%)  2 1/287 (0.35%)  1
Foot fracture  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Forearm fracture  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Graft complication  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hip fracture  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Incision site pain  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Incisional hernia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Joint dislocation  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Laceration  1  1/288 (0.35%)  2 0/287 (0.00%)  0
Overdose  1  3/288 (1.04%)  3 0/287 (0.00%)  0
Pelvic fracture  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Perirenal haematoma  1  0/288 (0.00%)  0 3/287 (1.05%)  3
Post procedural haematuria  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Procedural pain  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Psychosis postoperative  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Seroma  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Thermal burn  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Thoracic vertebral fracture  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Tibia fracture  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Transplant dysfunction  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Ureteric anastomosis complication  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Vascular pseudoaneurysm  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Wound dehiscence  1  3/288 (1.04%)  3 1/287 (0.35%)  1
Wound haematoma  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Investigations     
Alanine aminotransferase increased  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Aspartate aminotransferase increased  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Blood creatinine increased  1  10/288 (3.47%)  12 8/287 (2.79%)  9
Blood potassium increased  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Clostridium test positive  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Haemoglobin decreased  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Hepatic enzyme increased  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Histology abnormal  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Immunosuppressant drug level increased  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Mycobacterium test positive  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  3/288 (1.04%)  3 5/287 (1.74%)  7
Diabetes mellitus  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Diabetic ketoacidosis  1  2/288 (0.69%)  2 1/287 (0.35%)  1
Fluid overload  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Hypercalcaemia  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Hyperglycaemia  1  7/288 (2.43%)  7 2/287 (0.70%)  2
Hyperglycaemic hyperosmolar nonketotic syndrome  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hyperkalaemia  1  15/288 (5.21%)  16 5/287 (1.74%)  6
Hypernatraemia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hypoglycaemia  1  2/288 (0.69%)  2 1/287 (0.35%)  1
Hypokalaemia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hypomagnesaemia  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Hyponatraemia  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Hypophosphataemia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hypovolaemia  1  2/288 (0.69%)  2 1/287 (0.35%)  1
Lactic acidosis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Malnutrition  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Metabolic acidosis  1  0/288 (0.00%)  0 2/287 (0.70%)  2
Type 1 diabetes mellitus  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Back pain  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Cervical spinal stenosis  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Flank pain  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Intervertebral disc degeneration  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Mobility decreased  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Muscle haemorrhage  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Musculoskeletal pain  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Myalgia  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Osteitis  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Pain in extremity  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Vertebral foraminal stenosis  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Cholangiocarcinoma  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Diffuse large B-cell lymphoma  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Gastric cancer  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Malignant ascites  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Metastases to liver  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Papillary thyroid cancer  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Parathyroid tumour benign  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Post transplant lymphoproliferative disorder  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Renal cell carcinoma  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Nervous system disorders     
Carotid artery occlusion  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Central nervous system haemorrhage  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Central nervous system lesion  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Cerebrovascular accident  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Dizziness  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Headache  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Hypertensive encephalopathy  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Ischaemic stroke  1  1/288 (0.35%)  1 1/287 (0.35%)  1
Metabolic encephalopathy  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Myelopathy  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Neuropathy peripheral  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Posterior reversible encephalopathy syndrome  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Presyncope  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Status epilepticus  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Syncope  1  2/288 (0.69%)  2 3/287 (1.05%)  3
Product Issues     
Device dislocation  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Psychiatric disorders     
Alcohol withdrawal syndrome  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Mental status changes  1  2/288 (0.69%)  2 2/287 (0.70%)  3
Renal and urinary disorders     
Acute kidney injury  1  26/288 (9.03%)  33 31/287 (10.80%)  36
Azotaemia  1  2/288 (0.69%)  2 0/287 (0.00%)  0
Bladder outlet obstruction  1  0/288 (0.00%)  0 1/287 (0.35%)  1
Focal segmental glomerulosclerosis  1  2/288 (0.69%)  3 0/287 (0.00%)  0
Haematuria  1  2/288 (0.69%)  2 2/287 (0.70%)  2
Haemorrhage urinary tract  1  1/288 (0.35%)  1 0/287 (0.00%)  0
Hydronephrosis  1