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Efficacy and Safety of Everolimus in Liver Transplant Recipients of Living Donor Liver Transplants

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: NCT01888432
Recruitment Status : Completed
First Posted : June 27, 2013
Results First Posted : November 12, 2018
Last Update Posted : March 18, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Care Provider);   Primary Purpose: Treatment
Condition Liver Transplantation
Interventions Drug: Everolimus + reduced tacrolimus
Drug: Standard tacrolimus
Enrollment 285
Recruitment Details In all, 284 patients were randomized after transplantation to EVR+Reduced TAC group and TAC Control group. Two patients were not eligible and randomized in IRT by mistake and to whom no study medication was given, and so did not have their data included.
Pre-assignment Details A total of 494 patients were screened. Of these, 448 patients received a liver transplant and entered the run-in period.
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description Everolimus + reduced tacrolimus ± corticosteroids Standard tacrolimus ± corticosteroids
Period Title: 12-month Analysis (FAS)
Started 142 142
Completed 131 133
Not Completed 11 9
Reason Not Completed
Lost to Follow-up             0             2
Physician Decision             1             1
Withdrawal by Subject             6             3
Death             4             3
Period Title: 24-month Analysis (FAS)
Started 142 142
Completed 125 125
Not Completed 17 17
Reason Not Completed
Graft loss             0             1
Lost to Follow-up             0             2
Physician Decision             2             4
Withdrawal by Subject             7             6
Death             8             4
Period Title: 36-month Analysis (Extension)
Started 13 5
Completed 12 5
Not Completed 1 0
Reason Not Completed
Death             1             0
Arm/Group Title EVR+Reduced TAC TAC Control Total
Hide Arm/Group Description Everolimus + reduced tacrolimus ± corticosteroids Standard tacrolimus ± corticosteroids Total of all reporting groups
Overall Number of Baseline Participants 142 142 284
Hide Baseline Analysis Population Description
Full Analysis Set (FAS): patients were analyzed according to treatment assigned at randomization. Any subject without written informed consent signed did not have their data included. Mis-randomized patients, who were not eligible but randomized in IRT by mistake and to whom no study medication was given, did not have their data included.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 142 participants 142 participants 284 participants
54.2  (8.95) 52.7  (10.41) 53.5  (9.72)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 142 participants 142 participants 284 participants
Female
38
  26.8%
43
  30.3%
81
  28.5%
Male
104
  73.2%
99
  69.7%
203
  71.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 142 participants 142 participants 284 participants
Caucasian
30
  21.1%
30
  21.1%
60
  21.1%
Asian
111
  78.2%
112
  78.9%
223
  78.5%
Other
1
   0.7%
0
   0.0%
1
   0.4%
1.Primary Outcome
Title Number of Participants With Composite Efficacy Failure of Treated Biopsy Proven Acute Rejection, Graft Loss or Death in Everolimus With Reduced Tacrolimus Group Compared to Standard Tacrolimus
Hide Description Rate of composite efficacy failure of treated biopsy proven acute rejection (tBPAR ≥ RAI score 3), graft loss (GL) or death (D) in everolimus with reduced tacrolimus group compared to standard tacrolimus at 12 months
Time Frame 12 months post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
7
   4.9%
8
   5.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments non-inferior efficacy failure of the reduced tacrolimus regimen to control by rejecting the null hypothesis.
Type of Statistical Test Non-Inferiority
Comments HO: πT - πC ≥ 0.12 vs. HA: πT - πC < 0.12, where πT and πC are the true proportions of composite efficacy failure of tBPAR, GL, or D, (tBPAR/GL/D) at 12 months post-transplant for the respective treatment groups. The proportion of 0.12, or 12%, was pre-determined as the non-inferiority (NI) margin for composite efficacy failure.
Statistical Test of Hypothesis P-Value < 0.001
Comments Z-test p-value for non-inferiority test (non-inferiority margin = 12%) is for one-sided test and should be compared to 0.05 significance level.
Method Z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value -0.7
Confidence Interval (2-Sided) 90%
-5.2 to 3.7
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Renal Function by Estimated Glomerular Filtration Rate (eGFR) From Randomization
Hide Description Renal function (change in estimated glomerular filtration rate (eGFR)) from randomization to Month 12 post transplantation with everolimus (EVR) in combination with reduced tacrolimus (rTAC) compared to standard exposure tacrolimus (TAC) in living donor liver transplant recipients.
Time Frame From randomization to month 12
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Least Squares Mean (Standard Error)
Unit of Measure: mL/min/1.73 m^2
-7.94  (1.839) -12.09  (1.824)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments the null hypothesis below was tested at the one-sided α = 0.05 level: H0: μT - μC ≤ -6 mL/min/1.73 m2 vs. HA: μT - μC > -6 mL/min/1.73 m^2, where μT and μC are the true means of change in eGFR (MDRD-4) from randomization to Month 12 post-transplant for the reduced tacrolimus group and control group, respectively.
Statistical Test of Hypothesis P-Value < 0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.15
Confidence Interval (2-Sided) 90%
-0.09 to 8.40
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.574
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Compare Renal Function Over Time Assessed by the Change by eGFR, Post-randomization
Hide Description Change in renal function from randomization to month 24 assessed by the change in estimated GFR (MDRD-4). Rate of change of renal function.
Time Frame From randomziation to month 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Least Squares Mean (Standard Error)
Unit of Measure: mL/min/1.73 m2
-11.01  (1.928) -14.26  (1.914)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.25
Confidence Interval (2-Sided) 90%
-1.21 to 7.70
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.699
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With Composite of tBPAR, Graft Loss, and Death
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: incidence of a composite of tBPAR, graft loss, death
Time Frame Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
tBPAR/graft loss/death
12
   8.5%
11
   7.7%
On-treatment tBPAR/graft loss/death
7
   4.9%
9
   6.3%
5.Secondary Outcome
Title Compare Incidence of tBPAR
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: Incidence of tBPAR
Time Frame Month 12 and Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
tBPAR - month 12
3
   2.1%
5
   3.5%
tBPAR - month 24
4
   2.8%
6
   4.2%
On-treatment tBPAR - month 24
3
   2.1%
6
   4.2%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 12
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value -1.4
Confidence Interval (2-Sided) 90%
-4.7 to 2.0
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments tBPAR - month 24
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value -1.2
Confidence Interval (2-Sided) 90%
-5.1 to 2.6
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments On-treatment tBPAR - month 24
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value -2.1
Confidence Interval (2-Sided) 90%
-5.7 to 1.4
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
6.Secondary Outcome
Title Compare Incidence of BPAR
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: incidence of a composite of biopsy proven acute rejection (BPAR)
Time Frame Month 12 and Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
Month 12
7
   4.9%
6
   4.2%
Month 24
8
   5.6%
7
   4.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 12
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.9
Confidence Interval (2-Sided) 90%
-3.4 to 5.1
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 24
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 1.0
Confidence Interval (2-Sided) 90%
-3.6 to 5.6
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
7.Secondary Outcome
Title Compare Incidence of Graft Loss
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: incidence of graft loss
Time Frame Month 12 and Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
Month 12
0
   0.0%
0
   0.0%
month 24
0
   0.0%
1
   0.7%
month 24 (on-treatment graft loss)
0
   0.0%
0
   0.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments graft loss at month 24
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value -0.8
Confidence Interval (2-Sided) 90%
-2.1 to 0.5
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
8.Secondary Outcome
Title Compare Incidence of a Composite of Death or Graft Loss
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: Incidence of a composite of death or graft loss
Time Frame Month 12 and Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
Month 12
4
   2.8%
3
   2.1%
Month 24
8
   5.6%
5
   3.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 12
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.7
Confidence Interval (2-Sided) 90%
-2.5 to 3.8
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 24
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 2.3
Confidence Interval (2-Sided) 90%
-2.1 to 6.6
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
9.Secondary Outcome
Title Compare Incidence of Death
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: incidence of death
Time Frame Month 12 and Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
Month 12
4
   2.8%
3
   2.1%
Month 24
8
   5.6%
4
   2.8%
Month 24 (on-treatment death)
4
   2.8%
3
   2.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 12
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.7
Confidence Interval (2-Sided) 90%
-2.5 to 3.8
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 24
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 3.0
Confidence Interval (2-Sided) 90%
-1.1 to 7.2
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments Month 24 (On-treatment death)
Method of Estimation Estimation Parameter Kaplan-Meier
Estimated Value 0.7
Confidence Interval (2-Sided) 90%
-2.5 to 3.9
Estimation Comments KM rate and 90% CI are obtained using KM probability estimates of composite efficacy failure rates and standard error derived based on Greenwood’s formula.
10.Secondary Outcome
Title Compare Incidence of AR
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: incidence of acute rejection (AR)
Time Frame Month 12 and Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
Month 12
9
   6.3%
8
   5.6%
Month 24
12
   8.5%
9
   6.3%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.7
Confidence Interval (2-Sided) 90%
-3.9 to 5.3
Estimation Comments Month 12
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.1
Confidence Interval (2-Sided) 90%
-3.0 to 7.2
Estimation Comments Month 24
11.Secondary Outcome
Title Compare Incidence of tAR
Hide Description Compare between the treatment group EVR with rTAC vs standard TAC: incidence of treated acute rejection (tAR).
Time Frame Month 12 and Month 24 post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 142
Measure Type: Count of Participants
Unit of Measure: Participants
Month 12
5
   3.5%
6
   4.2%
Month 24
7
   4.9%
7
   4.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value -0.7
Confidence Interval (2-Sided) 90%
-4.5 to 3.1
Estimation Comments Month 12
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.0
Confidence Interval (2-Sided) 90%
-4.2 to 4.2
Estimation Comments Month 24
12.Secondary Outcome
Title Number of Participants With Time to Recurrence of HCC in Subjects With a Diagnosis of HCC at the Time of Liver Transplantation
Hide Description Patients transplanted for HCC or with HCC diagnosed at time of transplantation were monitored for HCC recurrence according to local practice. For example routine laboratory monitoring/tests, tumor markers, hepatic ultrasound, computed tomography scans (CAT, CT) or MRI (especially Fe-MRI) on a regular basis per local practice.
Time Frame Month 12 and Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 141
Measure Type: Count of Participants
Unit of Measure: Participants
HCC recurrence (n/M) - month 12 Number Analyzed 56 participants 62 participants
0
   0.0%
5
   8.1%
HCC recurrence (n/M) - month 24 Number Analyzed 56 participants 61 participants
1
   1.8%
6
   9.8%
13.Secondary Outcome
Title Number of Subjects Experiencing Adverse Events/Infections by SOC
Hide Description [Not Specified]
Time Frame Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 141
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE/infection
140
  98.6%
136
  96.5%
Blood and lymphatic system disorders
44
  31.0%
32
  22.7%
Cardiac disorders
15
  10.6%
12
   8.5%
Congenital, familial and genetic disorders
1
   0.7%
2
   1.4%
Ear and labyrinth disorders
2
   1.4%
5
   3.5%
Endocrine disorders
1
   0.7%
2
   1.4%
Eye disorders
17
  12.0%
15
  10.6%
Gastrointestinal disorders
98
  69.0%
74
  52.5%
General disorders&admin site conditions
48
  33.8%
42
  29.8%
Hepatobiliary disorders
44
  31.0%
40
  28.4%
Immune system disorders
8
   5.6%
11
   7.8%
Infections and infestations
84
  59.2%
70
  49.6%
Injury, poisoning&proced. complications
36
  25.4%
28
  19.9%
Investigations
61
  43.0%
68
  48.2%
Metabolism and nutrition disorders
87
  61.3%
60
  42.6%
Musculoskeletal and connective tissue disorders
30
  21.1%
43
  30.5%
Neoplasms benign, malig&unspecified (cysts&polyps)
10
   7.0%
17
  12.1%
Nervous system disorders
38
  26.8%
44
  31.2%
Product issues#
1
   0.7%
1
   0.7%
Psychiatric disorders
33
  23.2%
26
  18.4%
Renal and urinary disorders
46
  32.4%
36
  25.5%
Reproductive system&breast dis.
9
   6.3%
12
   8.5%
Respiratory, thoracic&mediastinal dis.
34
  23.9%
39
  27.7%
Skin&subcutaneous tissue disorders
39
  27.5%
44
  31.2%
Vascular disorders
38
  26.8%
30
  21.3%
14.Secondary Outcome
Title Compare Incidence of Notable Safety Events (SAEs, Infections and Serious Infections Leading to Premature Discontinuation)
Hide Description Notable events include death, Serious AE/infection,, and AE/infection leading to discontinuation of study medication.
Time Frame Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 142 141
Measure Type: Count of Participants
Unit of Measure: Participants
Any notable events
86
  60.6%
82
  58.2%
Death
8
   5.6%
4
   2.8%
Serious AE/Infection
83
  58.5%
78
  55.3%
AE/Infection lead. to premature disc of study med
21
  14.8%
18
  12.8%
15.Secondary Outcome
Title Composite Efficacy Failure of Treated Biopsy in Everolimus With Reduced Tacrolimus Group Compared to Standard Tacrolimus in Patients From Japan Only
Hide Description

Rate of composite efficacy failure of treated biopsy in everolimus with reduced tacrolimus group compared to standard tacrolimus from randomization in core study up to 36 months in the extension study.

Composite endpoint = treated BPAR, graft loss or death. AR = Acute rejection; tAR = treated AR; BPR = biopsy proven rejection; BPAR = biopsy proven acute rejection; tBPAR = treated BPAR

Time Frame randomization, 36 months post transplantion
Hide Outcome Measure Data
Hide Analysis Population Description
All extension patients consisted of all patients enrolled into this extension study.
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 16 12
Measure Type: Number
Unit of Measure: Participants
Composite endpoint 2 1
On-treatment composite endpoint 1 0
Graft loss/death 1 1
tBPAR 2 0
Graft loss 0 1
Death 1 0
AR 3 2
tAR 2 0
BPR 6 3
BPAR 3 2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 5.4
Confidence Interval (2-Sided) 95%
-19.9 to 30.6
Estimation Comments Composite endpoint
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Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 6.7
Confidence Interval (2-Sided) 95%
-6.0 to 19.3
Estimation Comments On-treatment composite endpoint
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Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 2.0
Confidence Interval (2-Sided) 95%
-24.6 to 28.7
Estimation Comments Graft loss/death
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Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 14.4
Confidence Interval (2-Sided) 95%
-4.2 to 33.1
Estimation Comments tBPAR
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Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 11.1
Confidence Interval (2-Sided) 95%
-9.4 to 31.6
Estimation Comments Death
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Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-28.9 to 35.2
Estimation Comments AR
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 14.4
Confidence Interval (2-Sided) 95%
-4.2 to 33.1
Estimation Comments tAR
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 14.9
Confidence Interval (2-Sided) 95%
-22.3 to 52.1
Estimation Comments BPR
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Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimate
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-28.9 to 35.2
Estimation Comments BPAR
16.Secondary Outcome
Title Renal Function by Estimated Glomerular Filtration Rate (All Extension Patients)
Hide Description Renal function (change in estimated glomerular filtration rate (eGFR)) from randomization to Month 36 post transplantation with everolimus (EVR) in combination with reduced tacrolimus (rTAC) compared to standard exposure tacrolimus (TAC) in living donor liver transplant recipients in Japan
Time Frame randomization, at 36 months post transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
All extension patients consisted of all patients enrolled into this extension study.
Arm/Group Title EVR+Reduced TAC TAC Control
Hide Arm/Group Description:
Everolimus + reduced tacrolimus ± corticosteroids
Standard tacrolimus ± corticosteroids
Overall Number of Participants Analyzed 13 5
Least Squares Mean (Standard Error)
Unit of Measure: mL/min/1.73m2
-26.88  (10.114) -16.87  (19.412)
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Statistical Analysis Overview Comparison Group Selection EVR+Reduced TAC, TAC Control
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -10.01
Confidence Interval (2-Sided) 95%
-59.91 to 39.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 22.059
Estimation Comments [Not Specified]
Time Frame Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 4 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title AE From Day 1 to Month 24_EVR+Reduced TAC AE From Day 1 to Month 24_TAC Control AE From Month 24 to Month 36_EVR+Reduced TAC AE From Month 24 to Month 36_TAC Control
Hide Arm/Group Description Everolimus + reduced tacrolimus ± corticosteroids Standard tacrolimus ± corticosteroids Everolimus + reduced tacrolimus ± corticosteroids Standard tacrolimus ± corticosteroids
All-Cause Mortality
AE From Day 1 to Month 24_EVR+Reduced TAC AE From Day 1 to Month 24_TAC Control AE From Month 24 to Month 36_EVR+Reduced TAC AE From Month 24 to Month 36_TAC Control
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   8/142 (5.63%)   4/141 (2.84%)   1/13 (7.69%)   0/5 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
AE From Day 1 to Month 24_EVR+Reduced TAC AE From Day 1 to Month 24_TAC Control AE From Month 24 to Month 36_EVR+Reduced TAC AE From Month 24 to Month 36_TAC Control
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   83/142 (58.45%)   78/141 (55.32%)   5/13 (38.46%)   0/5 (0.00%) 
Blood and lymphatic system disorders         
Anaemia  1  2/142 (1.41%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Leukocytosis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Leukopenia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Thrombocytopenia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Thrombotic microangiopathy  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cardiac disorders         
Acute myocardial infarction  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Angina pectoris  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Atrial fibrillation  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Bradycardia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cardiac arrest  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cardiac discomfort  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cardiac failure  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Cardiopulmonary failure  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Coronary artery disease  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Mitral valve incompetence  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Supraventricular tachycardia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Eye disorders         
Cataract  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Lens dislocation  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Gastrointestinal disorders         
Abdominal hernia  1  3/142 (2.11%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Abdominal incarcerated hernia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Abdominal pain  1  7/142 (4.93%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Abdominal pain upper  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Anal incontinence  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Ascites  1  0/142 (0.00%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Colitis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Constipation  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Crohn's disease  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Diarrhoea  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Duodenal perforation  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Duodenal ulcer  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Duodenal ulcer haemorrhage  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Enteritis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Gastric ulcer haemorrhage  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Gastrointestinal inflammation  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Haemorrhoids  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Ileus  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Ileus paralytic  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Incarcerated umbilical hernia  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Inguinal hernia  1  0/142 (0.00%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Intra-abdominal fluid collection  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Leukoplakia oral  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Mesenteric haemorrhage  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Nausea  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pancreatitis  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pancreatitis acute  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Parotid gland enlargement  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Peptic ulcer perforation  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pouchitis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Small intestinal haemorrhage  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Small intestine ulcer  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Strangulated umbilical hernia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Vomiting  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
General disorders         
Chest discomfort  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Chills  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Crepitations  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hyperpyrexia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Incarcerated hernia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Multiple organ dysfunction syndrome  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Non-cardiac chest pain  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Pyrexia  1  11/142 (7.75%)  8/141 (5.67%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatobiliary disorders         
Autoimmune hepatitis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Bile duct obstruction  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Bile duct stenosis  1  10/142 (7.04%)  6/141 (4.26%)  1/13 (7.69%)  0/5 (0.00%) 
Bile duct stone  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Biliary dilatation  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Biliary fistula  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Biloma  1  1/142 (0.70%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Cholangitis  1  8/142 (5.63%)  9/141 (6.38%)  0/13 (0.00%)  0/5 (0.00%) 
Cholangitis acute  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cholelithiasis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Cholelithiasis obstructive  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Dilatation intrahepatic duct acquired  1  1/142 (0.70%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatic artery thrombosis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatic function abnormal  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatic mass  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatic steatosis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatitis cholestatic  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Jaundice  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Jaundice cholestatic  1  0/142 (0.00%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Portal vein stenosis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Portal vein thrombosis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Primary biliary cholangitis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Immune system disorders         
Liver transplant rejection  1  3/142 (2.11%)  3/141 (2.13%)  0/13 (0.00%)  0/5 (0.00%) 
Transplant rejection  1  2/142 (1.41%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Infections and infestations         
Abdominal abscess  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Appendicitis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Arteriovenous graft site infection  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Bacterial infection  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Bacterial sepsis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Biliary tract infection  1  1/142 (0.70%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Bronchopulmonary aspergillosis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cellulitis  1  3/142 (2.11%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Clostridium difficile colitis  1  3/142 (2.11%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cytomegalovirus viraemia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Diarrhoea infectious  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Enterococcal bacteraemia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Epididymitis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Fungal sepsis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Gastroenteritis  1  4/142 (2.82%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Gastroenteritis norovirus  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Groin abscess  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatitis C  1  5/142 (3.52%)  3/141 (2.13%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatitis E  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Herpes zoster  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Infection  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Liver abscess  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Lower respiratory tract infection  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Orchitis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Peritonitis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pharyngitis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Pneumonia  1  10/142 (7.04%)  5/141 (3.55%)  0/13 (0.00%)  0/5 (0.00%) 
Pneumonia legionella  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Pneumonia viral  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Post procedural cellulitis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Post procedural sepsis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Postoperative wound infection  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Prostatic abscess  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pulmonary tuberculosis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Pyelonephritis acute  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Sepsis  1  1/142 (0.70%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Septic shock  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Staphylococcal bacteraemia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Systemic infection  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Tuberculosis  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Upper respiratory tract infection  1  3/142 (2.11%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Upper respiratory tract infection bacterial  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Urinary tract infection  1  1/142 (0.70%)  3/141 (2.13%)  0/13 (0.00%)  0/5 (0.00%) 
Urosepsis  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Injury, poisoning and procedural complications         
Anastomotic stenosis  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Biliary anastomosis complication  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Burns second degree  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Chemical peritonitis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Contusion  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Facial bones fracture  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Femoral neck fracture  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Graft loss  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Incarcerated incisional hernia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Incision site pain  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Incisional hernia  1  5/142 (3.52%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Multiple injuries  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Post procedural bile leak  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Post procedural haemorrhage  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Post procedural inflammation  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Procedural complication  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Procedural pain  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Spinal compression fracture  1  2/142 (1.41%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Spinal fracture  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Wound dehiscence  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Investigations         
Alanine aminotransferase increased  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Aspartate aminotransferase increased  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Blood alkaline phosphatase increased  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
C-reactive protein increased  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Gamma-glutamyltransferase increased  1  0/142 (0.00%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatic enzyme increased  1  4/142 (2.82%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Immunosuppressant drug level increased  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Liver function test increased  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Transaminases increased  1  1/142 (0.70%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Metabolism and nutrition disorders         
Diabetes mellitus  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Diabetes mellitus inadequate control  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Fluid overload  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Gout  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hyperglycaemia  1  1/142 (0.70%)  3/141 (2.13%)  0/13 (0.00%)  0/5 (0.00%) 
Hyperkalaemia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hypertriglyceridaemia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hypoalbuminaemia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hypokalaemia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hyponatraemia  1  2/142 (1.41%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Malnutrition  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Obesity  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Intervertebral disc protrusion  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Lumbar spinal stenosis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Musculoskeletal pain  1  0/142 (0.00%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Pain in extremity  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Spondylolisthesis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adenocarcinoma of colon  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Bone giant cell tumour  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatic angiosarcoma  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatocellular carcinoma  1  1/142 (0.70%)  4/141 (2.84%)  0/13 (0.00%)  0/5 (0.00%) 
Lipofibroma  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Lung neoplasm malignant  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Metastases to bone  1  0/142 (0.00%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Metastases to central nervous system  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Metastases to lung  1  0/142 (0.00%)  5/141 (3.55%)  0/13 (0.00%)  0/5 (0.00%) 
Metastases to spine  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Oropharyngeal cancer  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Prostate cancer  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Squamous cell carcinoma of the hypopharynx  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Squamous cell carcinoma of the oral cavity  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Nervous system disorders         
Altered state of consciousness  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Dizziness  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Headache  1  0/142 (0.00%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Hypoaesthesia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Migraine  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Neuropathy peripheral  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Restless legs syndrome  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Seizure  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Spondylitic myelopathy  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Tremor  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Wernicke's encephalopathy  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Psychiatric disorders         
Alcoholism  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Insomnia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Mental status changes  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Suicidal behaviour  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Renal and urinary disorders         
Acute kidney injury  1  2/142 (1.41%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Chromaturia  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Chronic kidney disease  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Haematuria  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Proteinuria  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Renal failure  1  2/142 (1.41%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Renal impairment  1  0/142 (0.00%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Acute pulmonary oedema  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Acute respiratory failure  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Cough  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Dyspnoea  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hypoxia  1  1/142 (0.70%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pharyngeal ulceration  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Pleural effusion  1  1/142 (0.70%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Pneumonia aspiration  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Pneumothorax  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pulmonary embolism  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pulmonary infarction  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Pulmonary mass  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Respiratory failure  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Wheezing  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Skin and subcutaneous tissue disorders         
Skin ulcer  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Vascular disorders         
Arterial haemorrhage  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Haematoma  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Hot flush  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Hypotension  1  1/142 (0.70%)  0/141 (0.00%)  0/13 (0.00%)  0/5 (0.00%) 
Lymphangiopathy  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Vena cava thrombosis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
Venous stenosis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  0/5 (0.00%) 
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AE From Day 1 to Month 24_EVR+Reduced TAC AE From Day 1 to Month 24_TAC Control AE From Month 24 to Month 36_EVR+Reduced TAC AE From Month 24 to Month 36_TAC Control
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   127/142 (89.44%)   122/141 (86.52%)   13/13 (100.00%)   4/5 (80.00%) 
Blood and lymphatic system disorders         
Anaemia  1  18/142 (12.68%)  15/141 (10.64%)  1/13 (7.69%)  0/5 (0.00%) 
Leukocytosis  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Leukopenia  1  16/142 (11.27%)  7/141 (4.96%)  0/13 (0.00%)  0/5 (0.00%) 
Nephrogenic anaemia  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Thrombocytopenia  1  14/142 (9.86%)  3/141 (2.13%)  0/13 (0.00%)  0/5 (0.00%) 
Endocrine disorders         
Cushingoid  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Eye disorders         
Cataract  1  8/142 (5.63%)  4/141 (2.84%)  0/13 (0.00%)  0/5 (0.00%) 
Conjunctival haemorrhage  1  1/142 (0.70%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  19/142 (13.38%)  12/141 (8.51%)  0/13 (0.00%)  0/5 (0.00%) 
Anal erosion  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Constipation  1  13/142 (9.15%)  16/141 (11.35%)  2/13 (15.38%)  1/5 (20.00%) 
Diarrhoea  1  32/142 (22.54%)  19/141 (13.48%)  2/13 (15.38%)  0/5 (0.00%) 
Enteritis  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  1/5 (20.00%) 
Mouth ulceration  1  17/142 (11.97%)  6/141 (4.26%)  0/13 (0.00%)  0/5 (0.00%) 
Nausea  1  7/142 (4.93%)  9/141 (6.38%)  1/13 (7.69%)  0/5 (0.00%) 
Stomatitis  1  19/142 (13.38%)  5/141 (3.55%)  1/13 (7.69%)  0/5 (0.00%) 
Vomiting  1  7/142 (4.93%)  10/141 (7.09%)  1/13 (7.69%)  0/5 (0.00%) 
General disorders         
Asthenia  1  1/142 (0.70%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Malaise  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Oedema peripheral  1  16/142 (11.27%)  8/141 (5.67%)  1/13 (7.69%)  0/5 (0.00%) 
Pyrexia  1  18/142 (12.68%)  20/141 (14.18%)  3/13 (23.08%)  1/5 (20.00%) 
Hepatobiliary disorders         
Hepatic steatosis  1  10/142 (7.04%)  7/141 (4.96%)  0/13 (0.00%)  0/5 (0.00%) 
Infections and infestations         
Acute sinusitis  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Cellulitis  1  1/142 (0.70%)  6/141 (4.26%)  0/13 (0.00%)  1/5 (20.00%) 
Conjunctivitis  1  2/142 (1.41%)  2/141 (1.42%)  1/13 (7.69%)  0/5 (0.00%) 
Gastroenteritis  1  1/142 (0.70%)  4/141 (2.84%)  2/13 (15.38%)  0/5 (0.00%) 
Gingivitis  1  1/142 (0.70%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Influenza  1  3/142 (2.11%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Nasopharyngitis  1  20/142 (14.08%)  16/141 (11.35%)  5/13 (38.46%)  3/5 (60.00%) 
Pharyngitis  1  1/142 (0.70%)  2/141 (1.42%)  2/13 (15.38%)  0/5 (0.00%) 
Pneumonia  1  4/142 (2.82%)  2/141 (1.42%)  2/13 (15.38%)  0/5 (0.00%) 
Sepsis  1  4/142 (2.82%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Tonsillitis  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Upper respiratory tract infection  1  18/142 (12.68%)  11/141 (7.80%)  0/13 (0.00%)  0/5 (0.00%) 
Injury, poisoning and procedural complications         
Contusion  1  1/142 (0.70%)  2/141 (1.42%)  2/13 (15.38%)  0/5 (0.00%) 
Hand fracture  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Heat stroke  1  0/142 (0.00%)  0/141 (0.00%)  2/13 (15.38%)  0/5 (0.00%) 
Incisional hernia  1  8/142 (5.63%)  2/141 (1.42%)  1/13 (7.69%)  0/5 (0.00%) 
Procedural pain  1  1/142 (0.70%)  1/141 (0.71%)  3/13 (23.08%)  0/5 (0.00%) 
Rib fracture  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Wound complication  1  2/142 (1.41%)  6/141 (4.26%)  0/13 (0.00%)  1/5 (20.00%) 
Investigations         
Alanine aminotransferase increased  1  5/142 (3.52%)  8/141 (5.67%)  1/13 (7.69%)  0/5 (0.00%) 
Aspartate aminotransferase increased  1  4/142 (2.82%)  6/141 (4.26%)  1/13 (7.69%)  0/5 (0.00%) 
Blood alkaline phosphatase increased  1  2/142 (1.41%)  4/141 (2.84%)  1/13 (7.69%)  0/5 (0.00%) 
Blood creatinine increased  1  10/142 (7.04%)  13/141 (9.22%)  0/13 (0.00%)  0/5 (0.00%) 
Gamma-glutamyltransferase increased  1  3/142 (2.11%)  5/141 (3.55%)  1/13 (7.69%)  0/5 (0.00%) 
Hepatic enzyme abnormal  1  8/142 (5.63%)  19/141 (13.48%)  0/13 (0.00%)  0/5 (0.00%) 
Hepatic enzyme increased  1  16/142 (11.27%)  19/141 (13.48%)  0/13 (0.00%)  0/5 (0.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  9/142 (6.34%)  13/141 (9.22%)  0/13 (0.00%)  0/5 (0.00%) 
Dehydration  1  3/142 (2.11%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Dyslipidaemia  1  13/142 (9.15%)  4/141 (2.84%)  0/13 (0.00%)  0/5 (0.00%) 
Hypercholesterolaemia  1  22/142 (15.49%)  2/141 (1.42%)  0/13 (0.00%)  0/5 (0.00%) 
Hyperkalaemia  1  20/142 (14.08%)  13/141 (9.22%)  0/13 (0.00%)  0/5 (0.00%) 
Hyperlipidaemia  1  22/142 (15.49%)  8/141 (5.67%)  0/13 (0.00%)  0/5 (0.00%) 
Hyperuricaemia  1  7/142 (4.93%)  8/141 (5.67%)  2/13 (15.38%)  0/5 (0.00%) 
Hypoalbuminaemia  1  7/142 (4.93%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Hypokalaemia  1  10/142 (7.04%)  3/141 (2.13%)  1/13 (7.69%)  0/5 (0.00%) 
Hypomagnesaemia  1  10/142 (7.04%)  11/141 (7.80%)  0/13 (0.00%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  5/142 (3.52%)  9/141 (6.38%)  1/13 (7.69%)  0/5 (0.00%) 
Arthritis  1  1/142 (0.70%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Back pain  1  8/142 (5.63%)  10/141 (7.09%)  1/13 (7.69%)  0/5 (0.00%) 
Joint swelling  1  0/142 (0.00%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Lumbar spinal stenosis  1  0/142 (0.00%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Nervous system disorders         
Dizziness  1  3/142 (2.11%)  9/141 (6.38%)  0/13 (0.00%)  0/5 (0.00%) 
Headache  1  19/142 (13.38%)  14/141 (9.93%)  1/13 (7.69%)  0/5 (0.00%) 
Paralysis  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Post herpetic neuralgia  1  0/142 (0.00%)  1/141 (0.71%)  0/13 (0.00%)  1/5 (20.00%) 
Tremor  1  4/142 (2.82%)  11/141 (7.80%)  0/13 (0.00%)  0/5 (0.00%) 
Psychiatric disorders         
Depression  1  2/142 (1.41%)  8/141 (5.67%)  0/13 (0.00%)  0/5 (0.00%) 
Insomnia  1  26/142 (18.31%)  13/141 (9.22%)  1/13 (7.69%)  0/5 (0.00%) 
Renal and urinary disorders         
Calculus urinary  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Chronic kidney disease  1  4/142 (2.82%)  6/141 (4.26%)  1/13 (7.69%)  0/5 (0.00%) 
Proteinuria  1  6/142 (4.23%)  2/141 (1.42%)  1/13 (7.69%)  0/5 (0.00%) 
Renal failure  1  3/142 (2.11%)  13/141 (9.22%)  0/13 (0.00%)  0/5 (0.00%) 
Renal impairment  1  11/142 (7.75%)  5/141 (3.55%)  0/13 (0.00%)  0/5 (0.00%) 
Reproductive system and breast disorders         
Dysmenorrhoea  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Atelectasis  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Cough  1  12/142 (8.45%)  15/141 (10.64%)  0/13 (0.00%)  0/5 (0.00%) 
Pneumothorax  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Rhinitis allergic  1  2/142 (1.41%)  2/141 (1.42%)  1/13 (7.69%)  0/5 (0.00%) 
Skin and subcutaneous tissue disorders         
Dry skin  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Eczema asteatotic  1  1/142 (0.70%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Keloid scar  1  1/142 (0.70%)  1/141 (0.71%)  1/13 (7.69%)  0/5 (0.00%) 
Pruritus  1  22/142 (15.49%)  18/141 (12.77%)  1/13 (7.69%)  0/5 (0.00%) 
Rash  1  7/142 (4.93%)  10/141 (7.09%)  0/13 (0.00%)  0/5 (0.00%) 
Skin ulcer  1  0/142 (0.00%)  0/141 (0.00%)  1/13 (7.69%)  0/5 (0.00%) 
Urticaria  1  1/142 (0.70%)  2/141 (1.42%)  1/13 (7.69%)  0/5 (0.00%) 
Vascular disorders         
Hypertension  1  29/142 (20.42%)  23/141 (16.31%)  1/13 (7.69%)  0/5 (0.00%) 
1
Term from vocabulary, MedDRA (21.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01888432     History of Changes
Other Study ID Numbers: CRAD001H2307
2010-024527-25 ( EudraCT Number )
First Submitted: June 15, 2013
First Posted: June 27, 2013
Results First Submitted: October 5, 2018
Results First Posted: November 12, 2018
Last Update Posted: March 18, 2019