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Study Evaluating The Effect Of Ramipril On Urinary Protein Excretion In Renal Transplant Patients Converted To Sirolimus

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ClinicalTrials.gov Identifier: NCT00502242
Recruitment Status : Completed
First Posted : July 17, 2007
Results First Posted : August 27, 2014
Last Update Posted : August 27, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Kidney Transplant
Intervention Drug: ramipril
Enrollment 229
Recruitment Details A Randomized, Placebo Controlled, Double-Blind Comparative Study Evaluating the Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus.
Pre-assignment Details Eligible participants were randomly assigned in a Double-Blind fashion to the Ramipril treatment group or the Placebo control group.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description Participants were receiving cyclosporine (CsA) or tacrolimus (TAC) and either mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) or steroids dosed per center’s standard of care. Participants received ramipril, 5 or 10 milligrams per day (mg/d) orally (PO). 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of sirolimus [SRL] initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 nanograms per milliliter [ng/mL] less than [<]1 year post-transplant [PT], 5-15 ng/mL greater than or equal to [≥]1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if urinary protein to creatinine ratio (U p/c) was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study. Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Period Title: Overall Study
Started 155 140
Completed 104 84
Not Completed 51 56
Reason Not Completed
Lack of Efficacy             1             11
Adverse Event             31             20
Physician Decision             2             3
Other - Unspecified             8             14
Protocol Violation             3             1
Withdrawal by Subject             6             7
Arm/Group Title Ramipril Placebo Total
Hide Arm/Group Description Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study. Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study. Total of all reporting groups
Overall Number of Baseline Participants 155 140 295
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 155 participants 140 participants 295 participants
46.8  (12.7) 47.5  (12.9) 47.1  (12.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 155 participants 140 participants 295 participants
Female
48
  31.0%
50
  35.7%
98
  33.2%
Male
107
  69.0%
90
  64.3%
197
  66.8%
1.Primary Outcome
Title Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL
Hide Description The event for each participant was defined as the initiation of losartan while on SRL and ramipril/placebo combination therapy. Participants who started losartan prior to SRL administration were not counted as events. Percentage was estimated using Kaplan-Meier method for time to event data.
Time Frame From Day 1 of SRL conversion to 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Modified Intent to Treat (mITT) population: all participants in the safety population who took at least one dose of SRL.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
6.2
(2.7 to 11.6)
23.2
(15.7 to 31.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments 2-sided p-value; alpha equals (=) 0.05
Method Log Rank
Comments Stratified log-rank test with region and race strata
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.228
Confidence Interval (2-Sided) 95%
0.099 to 0.528
Estimation Comments Stratified Cox proportional hazard model with region and race strata
2.Secondary Outcome
Title Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL
Hide Description Defined as the time from the first dose of SRL administration to the first dose escalation of randomized test article (ramipril or placebo; in weeks), or censored on the day that a participant stopped the combination of SRL and randomized test article (ramipril or placebo) if the participants did not experience any ramipril/placebo dose escalation following conversion to SRL. Dose-escalation was defined as an increase in total daily dose of ramipril/placebo compared to Day 1 post conversion. Percentage was estimated using Kaplan-Meier method for time to event data.
Time Frame From Day 1 of SRL conversion to 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
14.4
(8.7 to 21.3)
29.2
(21.2 to 37.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0031
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Log Rank
Comments Stratified log-rank test with region and race strata
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.425
Confidence Interval (2-Sided) 95%
0.237 to 0.763
Estimation Comments Stratified Cox proportional hazard model with region and race strata
3.Secondary Outcome
Title Percentage of Participants With U p/c <0.5 at 24 and 52 Weeks Following Conversion to Sirolimus
Hide Description Spot urine sample of protein and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.
Time Frame 24 weeks and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; includes assessments from On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Unit of Measure: percentage of participants
Up to 24 weeks post-conversion 92.0 77.8
Up to 52 weeks post-conversion 82.6 73.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 24 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 52 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With Urinary Albumin to Creatinine Ratio (U Alb/c) <0.5 at 24 and 52 Weeks Following Conversion to SRL
Hide Description Spot urine sample of albumin and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.
Time Frame 24 weeks and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; includes assessments from On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Unit of Measure: percentage of participants
Up to 24 weeks post-conversion 95.7 89.7
Up to 52 weeks post-conversion 88.4 82.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 24 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.093
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 52 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.219
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
5.Secondary Outcome
Title Percentage of Participants With Both U Alb/c <0.5 and U p/c <0.5 at 24 and 52 Weeks Following Conversion to SRL
Hide Description The U alb/c and U p/c must have been collected on the same day to be counted as the numerator.
Time Frame 24 weeks and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; includes assessments from On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Unit of Measure: percentage of participants
Up to 24 weeks post-conversion 91.3 77.0
Up to 52 weeks post-conversion 79.0 70.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 24 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 52 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
6.Secondary Outcome
Title U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
Hide Description U p/c was measured in milligrams per milligram (mg/mg). The baseline U p/c values were the last values of the pre-SRL conversion period.
Time Frame Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; n (number) = number of participants assessed for the specified parameter at a given visit; only participants with nonmissing records of U p/c were included in the analysis. Includes measures collected from On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Mean (Standard Deviation)
Unit of Measure: mg/mg
Baseline (n=138,126) 0.17  (0.37) 0.15  (0.07)
Week 3 (n=130,117) 0.18  (0.11) 0.23  (0.19)
Week 4 (n=136,124) 0.18  (0.09) 0.28  (0.27)
Week 8 (n=130,119) 0.23  (0.39) 0.31  (0.37)
Week 12 (n=124,121) 0.23  (0.30) 0.38  (1.18)
Week 24 (n=121,122) 0.26  (0.40) 0.31  (0.39)
Week 30 (n=111,108) 0.23  (0.23) 0.32  (0.37)
Week 36 (n=109,92) 0.22  (0.13) 0.29  (0.30)
Week 52 (n=126,111) 0.27  (0.31) 0.35  (0.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 3, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.16
Estimation Comments Adjusted for baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 3, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.36
Estimation Comments Adjusted for baseline
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from baseline at Week 3, Ramipril versus (vs.) Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0098
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.76 to 0.96
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from baseline at Week 4, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.18
Estimation Comments Adjusted for baseline
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from baseline at Week 4, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.52
Estimation Comments Adjusted for baseline
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from baseline at Week 4, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.68 to 0.89
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from baseline at Week 8, Ramipirl
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.27
Estimation Comments Adjusted for baseline
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from baseline at Week 8, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.61
Estimation Comments Adjusted for baseline
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 8, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0016
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.68 to 0.91
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 12, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.34
Estimation Comments Adjusted for baseline
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 12, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.63
Estimation Comments Adjusted for baseline
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 12, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0165
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.70 to 0.96
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 24, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.48
Estimation Comments Adjusted for baseline
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 24, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.78
Estimation Comments Adjusted for baseline
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 24, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0264
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.70 to 0.98
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 30, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.43
Estimation Comments Adjusted for baseline
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 30, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.82
Estimation Comments Adjusted for baseline
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 30, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.66 to 0.93
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 36, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.40
Estimation Comments Adjusted for baseline
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 36, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.67
Estimation Comments Adjusted for baseline
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 36, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0341
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.72 to 0.99
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 52, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.56
Estimation Comments Adjusted for baseline
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 52, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.86
Estimation Comments Adjusted for baseline
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 52, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0600
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic Up/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.70 to 1.01
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
7.Secondary Outcome
Title U Alb/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
Hide Description U alb/c was measured in mg/mg. Baseline U alb/c values were the last values of the pre-SRL conversion period.
Time Frame Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; n=number of participants assessed for the specified parameter at a given visit; only participants with nonmissing records of U alb/c were included in the analysis. Includes measures collected from On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Mean (Standard Deviation)
Unit of Measure: mg/mg
Baseline (n=138,126) 0.04  (0.26) 0.02  (0.02)
Week 3 (n=129,117) 0.03  (0.05) 0.06  (0.11)
Week 4 (n=136,124) 0.03  (0.04) 0.09  (0.16)
Week 8 (n=129,119) 0.06  (0.31) 0.11  (0.24)
Week 12 (n=124,121) 0.05  (0.09) 0.17  (0.84)
Week 24 (n=121,122) 0.08  (0.24) 0.11  (0.28)
Week 30 (n=111,108) 0.06  (0.13) 0.11  (0.21)
Week 36 (n=109,92) 0.05  (0.08) 0.10  (0.21)
Week 52 (n=126,111) 0.09  (0.21) 0.15  (0.31)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 3, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.46
Estimation Comments Adjusted for baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 3, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.05
Estimation Comments Adjusted for baseline
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 3, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0034
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.57 to 0.89
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 4, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.43
Estimation Comments Adjusted for baseline
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 4, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.37
Estimation Comments Adjusted for baseline
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 4, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.47 to 0.76
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 8, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.67
Estimation Comments Adjusted for baseline
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 8, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.74
Estimation Comments Adjusted for baseline
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 8, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.47 to 0.79
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 12, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 1.91
Estimation Comments Adjusted for baseline
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 12, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.92
Estimation Comments Adjusted for baseline
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 12, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0032
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.49 to 0.87
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 24, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.33
Estimation Comments Adjusted for baseline
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 24, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 3.39
Estimation Comments Adjusted for baseline
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 24, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0130
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.51 to 0.92
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 30, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.50
Estimation Comments Adjusted for baseline
Show Statistical Analysis 17 Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 30, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 3.39
Estimation Comments Adjusted for baseline
Show Statistical Analysis 18 Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 30, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0577
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.54 to 1.01
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 19 Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 36, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.52
Estimation Comments Adjusted for baseline
Show Statistical Analysis 20 Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 36, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 3.27
Estimation Comments Adjusted for baseline
Show Statistical Analysis 21 Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 36, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1146
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.56 to 1.07
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
Show Statistical Analysis 22 Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Ramipril
Comments Change from Baseline at Week 52, Ramipril
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 2.92
Estimation Comments Adjusted for baseline
Show Statistical Analysis 23 Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection Placebo
Comments Change from Baseline at Week 52, Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Geometric Mean Fold Change
Estimated Value 3.45
Estimation Comments Adjusted for baseline
Show Statistical Analysis 24 Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 52, Ramipril vs. Placebo
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3496
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with change in the logarithmic U alb/c as dependent variable, treatment and region/race as factors, and logarithmic baseline as covariate
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.60 to 1.20
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.
8.Secondary Outcome
Title Percentage of Participants Who Discontinued SRL Therapy at 24 and 52 Weeks Following Conversion to SRL
Hide Description Defined as the percentage of participants who stop SRL (as test article) between the first day of SRL and either Week 24 or Week 52 following conversion to SRL. If a participant had a >14 day gap in SRL use, the stop date of SRL was the date of the last SRL use before it was re-initiated. Participants who early terminate SRL at Week 24 were defined as having SRL stop day less than or equal to (≤) Day 190 (selected as the midpoint between Weeks 24 and 30). Participants who early terminate SRL at Week 52 were defined as having SRL stop day ≤Day 337 (selected as the midpoint between Weeks 44 and 52).
Time Frame 24 weeks and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Unit of Measure: percentage of participants
Up to 24 weeks post-conversion 15.2 15.9
Up to 52 weeks post-conversion 19.6 28.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 24 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.0000
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Up to 52 weeks post-conversion
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1115
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
9.Secondary Outcome
Title Abbreviated Modified Diet in Renal Disease (MDRD) Glomerular Filtration Rate (GFR) at Weeks 12, 24, and 52 Following Conversion to SRL
Hide Description Calculated in millimeters per minute per 1.73 square meters (mL/min/1.73m^2). Age and corresponding creatinine at each visit (Weeks 12, 24, and 52) were used to calculate GFR.
Time Frame 12, 24, and 52 weeks following conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; n=number of participants assessed for the specified parameter at a given visit. Includes measures collected from On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73 m^2
Baseline (n=138,126) 62.06  (14.08) 63.30  (15.64)
Week 12 (n=125,122) 64.91  (16.54) 66.58  (15.26)
Week 24 (n=123,122) 65.18  (17.99) 63.85  (16.49)
Week 52 (n=128,115) 64.17  (16.79) 63.41  (15.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4933
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with MDRD change as dependent variable, treatment and region/race as factors, and baseline as covariate.
Method of Estimation Estimation Parameter Adjusted LS Mean Difference
Estimated Value -0.86
Confidence Interval (2-Sided) 95%
-3.33 to 1.61
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.26
Estimation Comments Adjusted for baseline
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0888
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with MDRD change as dependent variable, treatment and region/race as factors, and baseline as covariate.
Method of Estimation Estimation Parameter Adjusted LS Mean Difference
Estimated Value 2.48
Confidence Interval (2-Sided) 95%
-0.38 to 5.33
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.45
Estimation Comments Adjusted for baseline
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Change from Baseline at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1475
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA model with MDRD change as dependent variable, treatment and region/race as factors, and baseline as covariate
Method of Estimation Estimation Parameter Adjusted LS Mean Difference
Estimated Value 2.12
Confidence Interval (2-Sided) 95%
-0.75 to 4.99
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.46
Estimation Comments Adjusted for baseline
10.Secondary Outcome
Title Fraction of Albumin (Milligrams Per Deciliter [mg/dL]) to Protein (mg/dL) in Urine at 24 and 52 Weeks After Conversion to SRL
Hide Description Baseline fraction was the last value of the pre-SRL conversion period. Only the last value of U p/c or U alb/c was used for analysis if multiple measurements occurred in the same data anlysis interval. Fraction of albumin and protein was calculated only when urine protein was 6.2 mg/dL or higher. For urine albumin, if the value was reported as '<xx.x', the numerical portion of the value was used in the calculation of fraction of albumin and protein.
Time Frame 24 weeks and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; n=number of participants assessed for the specified parameter at a given visit. Includes measures collected from On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 111 110
Mean (Standard Deviation)
Unit of Measure: (mg/dL)/(mg/dL)
Week 24 (n=104,110) 0.19  (0.17) 0.25  (0.19)
Week 52 (n=111,105) 0.22  (0.18) 0.25  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1167
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments Log (Fraction of albumin to protein in urine) as dependent variable, treatment and region/race as factor, and Log(baseline) as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 0.84
Confidence Interval (2-Sided) 95%
0.68 to 1.04
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7519
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments Log (Fraction of albumin to protein in urine) as dependent variable, treatment and region/race as factor, and Log(baseline) as covariate.
Method of Estimation Estimation Parameter Treatment Ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.82 to 1.31
Estimation Comments Treatment ratio (Ramipril/Placebo) in the geometric mean.
11.Secondary Outcome
Title Percentage of Participants With Potentially Clinically Important Blood Pressure (BP) Values by Diastolic and Systolic BP Category
Hide Description BP values of potential clinical importance were recorded and categorized as follows: diastolic BP (DBP) ≤50 millimeters of mercury (mmHg) or ≥110 mmHg and systolic BP (SBP) ≤90 mmHg and ≥180 mmHg. Data were summarized for the on-therapy period and the off-therapy period and for the pre-SRL period.
Time Frame Baseline, Pre-SRL (from first dose of ramipril/placebo up to SRL conversion), On-Therapy (up to 52 weeks after SRL conversion), and Off-Therapy Period (up to 56 weeks after SRL conversion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
Baseline, Low DBP ≤50 mmHg (n=155,140) 0.0 0.7
Baseline, Low SBP: ≤90 mmHg (n=155,140) 0.0 0.7
Pre-SRL, Low DBP: ≤50 mmHg (n=152,135) 0.0 0.7
Pre-SRL, High DBP: ≥110 mmHg (n=152,135) 0.0 1.5
Pre-SRL, Low SBP: ≤90 mmHg (n=152,135) 0.0 0.7
Pre-SRL, High SBP: ≥180 mmHg (n=152,135) 0.7 0.7
On Therapy, Low DBP: ≤50 mmHg (n=138,126) 3.6 2.4
On Therapy, High DBP: ≥110 mmHg (n=138,126) 0.0 1.6
On Therapy, Low SBP: ≤90 mmHg (n=138,126) 3.6 4.0
On Therapy, High SBP: ≥180 mmHg (n=138,126) 0.7 4.0
Off Therapy, High DBP ≥110 mmHg (n=35,69) 2.9 1.4
Off Therapy, Low SBP: ≤90 mmHg (n=35,69) 2.9 1.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL, Low DBP ≤50 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.470
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL, High DBP ≥110 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.220
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL, Low SBP: ≤90 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.470
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL, High SBP: ≥180 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On Therapy, Low DBP ≤50 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.725
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On Therapy, High DBP ≥110 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.227
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On Therapy, Low SBP: ≤90 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On Therapy, High SBP: ≥180 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.106
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Off Therapy, High DBP ≥110 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Off Therapy, Low SBP: ≤90 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Baseline, Low DBP ≤50 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.475
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Baseline, Low SBP: ≤90 mmHg
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.475
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
12.Secondary Outcome
Title SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval
Hide Description Cmin,TN was determined for SRL using the area method for the intervals: 0–2 weeks, >2–4 weeks, >4–12 weeks, >12–24 weeks, >24–36 weeks and >36–52 weeks using the equation:Cmin,TN = AUCi-j/timej-timeiwhere AUC is the area under the concentration-time curve, i is the beginning of the interval and j is the end of the interval. Cmin,TN was calculated for participants who did not dropout of studies, but were missing concentrations at the interval endpoints by carrying the last observed concentration forward to the interval endpoint.
Time Frame From Day 1 of SRL conversion to 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population; n=number of participants assessed for the specified parameter for the given time interval; only participants dosed throughout the interval were included.
Arm/Group Title Ramipril
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 258
Mean (Standard Deviation)
Unit of Measure: ng/mL
0-2 weeks (n=258) 9.853  (6.0250)
>2-4 weeks (n=257) 9.872  (4.1408)
>4-12 weeks (n=256) 9.273  (3.1763)
>12-24 weeks (n=244) 9.274  (2.8944)
>24-36 weeks (n=226) 9.316  (3.1535)
>36-52 weeks (n=193) 8.961  (2.9031)
0-52 weeks (n=264) 9.300  (2.2678)
13.Secondary Outcome
Title Percentage of Participants With Hemoglobin Levels ≤100 Grams Per Liter (g/L)
Hide Description [Not Specified]
Time Frame Baseline, Pre-SRL (from first dose of ramipril/placebo up to SRL conversion), On-Therapy (up to 52 weeks after SRL conversion), and Off-Therapy Period (up to 56 weeks after SRL conversion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (n=155,140) 1.3 1.4
Pre-SRL (n=148,129) 2.0 0.8
On-Therapy (n=138,124) 17.4 12.1
Off-Therapy (n=33,34) 9.1 2.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.626
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.297
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Off-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.356
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
14.Secondary Outcome
Title Percentage of Participants Using Red Blood Cell Production Stimulants (Erythropoiesis Stimulating Agents [ESAs])
Hide Description [Not Specified]
Time Frame Baseline, Pre-SRL (from first dose of ramipril/placebo up to SRL conversion), On-Therapy (up to 52 weeks after SRL conversion), and Off-Therapy Period (up to 56 weeks after SRL conversion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population; n=number of participants analyzed for the specified parameter at a given visit.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (n=155,140) 5.8 1.4
Pre-SRL (n=155,140) 4.5 0.7
On-Therapy (n=138,126) 4.3 3.2
Off-Therapy (n=136,122) 1.5 4.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.064
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.752
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Off-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.261
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
15.Secondary Outcome
Title Change From Baseline in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) at 4, 12, 24, and 52 Weeks Following Conversion to SRL
Hide Description Parameters assessed included (all fasting) total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-densitylipoprotein cholesterol (HDL-C).
Time Frame 4, 12, 24, and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population; n=number of participants assessed for the specified parameter at a given visit.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 128 109
Mean (Standard Error)
Unit of Measure: mmol/L
TC, Week 4 (n=128,109) 0.83  (0.06) 0.91  (0.09)
TC, Week 12 (n=115,108) 0.94  (0.09) 0.92  (0.10)
TC, Week 24 (n=105,102) 0.91  (0.12) 0.87  (0.09)
TC, Week 52 (n=94,79) 0.84  (0.11) 0.69  (0.12)
HDL-C, Week 4 (n=125,107) 0.06  (0.02) 0.09  (0.03)
HDL-C, Week 12 (n=114,104) 0.03  (0.02) 0.03  (0.02)
HDL-C, Week 24 (n=102,100) 0.07  (0.03) 0.04  (0.03)
HDL-C, Week 52 (n=92,78) 0.12  (0.03) 0.06  (0.04)
LDL-C, Week 4 (n=123,100) 0.59  (0.06) 0.56  (0.07)
LDL-C, Week 12 (n=109,96) 0.66  (0.08) 0.53  (0.08)
LDL-C, Week 24 (n=96,95) 0.66  (0.10) 0.56  (0.08)
LDL-C, Week 52 (n=90,73) 0.56  (0.10) 0.27  (0.09)
Triglycerides, Week 4 (n=127,108) 0.41  (0.07) 0.65  (0.10)
Triglycerides, Week 12 (n=114,107) 0.59  (0.10) 0.79  (0.11)
Triglycerides, Week 24 (n=104,102) 0.54  (0.11) 0.72  (0.13)
Triglycerides, Week 52 (n=93,77) 0.44  (0.10) 0.58  (0.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments TC, Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.381
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.09
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments TC, Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.956
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments TC, Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.903
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in adjusted means
Estimated Value 0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.14
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments TC, Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.503
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments HDL-C, Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.451
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments HDL-C, Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.919
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.03
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments HDL-C, Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.637
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.04
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments HDL-C, Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.229
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.05
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments LDL-C, Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.766
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.03
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments LDL-C, Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.217
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.11
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments LDL-C, Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.457
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.10
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments LDL-C, Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.041
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value 0.26
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.13
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Triglycerides, Week 4
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.12
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Triglycerides, Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.180
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.20
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.15
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Triglycerides, Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.264
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.19
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 16 Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Triglycerides, Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.408
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method ANCOVA
Comments ANCOVA with treatment as a factor and baseline as a covariate
Method of Estimation Estimation Parameter Difference in Adjusted Means
Estimated Value -0.14
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event
Hide Description BCAR was defined according to updated Banff criteria (1997)for renal allograft rejection. The time to the first BCAR was defined as the date of first BCAR to the date of the first dose of SRL (in weeks). Participants without BCAR were censored at the time of withdrawal from the study.
Time Frame From Day 1 of SRL conversion to 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; includes BCAR occurring in On-Therapy and Off-Therapy Periods.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Unit of Measure: participants
13 5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0732
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.487
Confidence Interval (2-Sided) 95%
0.887 to 6.978
Estimation Comments Hazard ratio was based on the Cox proportional hazards model.
17.Secondary Outcome
Title Percentage of Participants With First BCAR at 24 and 52 Weeks Following Conversion to SRL
Hide Description BCAR was defined according to updated Banff criteria (1997)for renal allograft rejection. Participants without BCAR were censored at the time of withdrawal from the study. Defined as the first BCAR occurring on therapy following conversion to SRL based on the mITT population. Time to first BCAR was defined as the date of first BCAR to date of the first dose of SRL (in weeks). Percentages were estimated using the Kaplan-Meier method for time to event data.
Time Frame 24 weeks and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; includes BCAR occurring in the On-Therapy and Off-Therapy Periods
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
24 weeks post-conversion
8.0
(4.2 to 13.3)
0.8
(0.1 to 4.0)
52 weeks post-conversion
9.5
(5.3 to 15.1)
3.2
(1.1 to 7.5)
18.Secondary Outcome
Title Number of Participants With BCAR by Severity of First BCAR
Hide Description Severity was summarized by type (antibody versus T-cell) and by phase: post-SRL (where both on-therapy and off-therapy events are included) and post-SRL (on-therapy). BCAR was categorized using Banff criteria as antibody-mediated (AM) or T-cell. AM BCAR severity was graded as Grade I (mild), Grade II (moderate [mod]), and Grade III (severe). T-cell BCAR severity was graded as 'Grade Ia, Ib (mild), Grade IIa, IIb (mod), and Grade III (severe). If a participant had both T-cell BCAR and antibody-mediated BCAR on the first rejection, the participant was counted in each category. For participants with T-cell BCAR (post-SRL and post-SRL On -Therapy) the p-value could not be calculated and all events were mild in severity.
Time Frame From Day 1 of SRL conversion to 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population; only participants with BCAR were included in the anlaysis.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 13 8
Measure Type: Number
Unit of Measure: participants
Post-SRL, AM BCAR, Grade I (mild) 1 2
Post-SRL, AM BCAR, Grade II (mod) 0 1
Post-SRL, AM BCAR, Grade III (severe) 0 1
Post-SRL, T-Cell BCAR, Grade I (mild) 12 4
Post-SRL (On-Therapy), AM BCAR, Grade I (mild) 1 1
Post-SRL (On-Therapy), AM BCAR, Grade II (mod) 0 1
Post-SRL (On-Therapy), T-Cell BCAR, Grade I (mild) 10 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Post-SRL, AM BCAR
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7165
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel row mean test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Post-SRL (On-Therapy), AM BCAR
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4795
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Cochran-Mantel-Haenszel
Comments Cochran-Mantel-Haenszel row mean test
19.Secondary Outcome
Title Percentage of Participants With Graft Loss at 24 and 52 Weeks Following Conversion to SRL
Hide Description Graft loss was defined as physical loss (nephrectomy orretransplantation), functional loss (requiring dialysis for ≥56days with no return of graft function), or death.
Time Frame 24 weeks and 52 weeks after conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
mITT population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 138 126
Measure Type: Number
Unit of Measure: percentage of participants
Week 24 0.0 0.0
Week 52 0.0 0.8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4773
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
20.Secondary Outcome
Title Percentage of Participants Using Statins
Hide Description [Not Specified]
Time Frame Baseline, Pre-SRL (from first dose of ramipril/placebo up to SRL conversion), On-Therapy (up to 52 weeks after SRL conversion), and Off-Therapy Period (up to 56 weeks after SRL conversion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population; n=number of participants analyzed for the specified parameter at a given visit.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (n=155,140) 45.8 36.4
Pre-SRL (n=155,140) 45.2 40.0
On-Therapy (n=138,126) 67.4 72.2
Off-Therapy (n=136,122) 62.5 68.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.410
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.423
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Off-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.297
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
21.Secondary Outcome
Title Percentage of Participants With an Infection
Hide Description Includes treatment-emergent adverse events based on categorization by the investigator as 'infection', regardless of the event preferred term in Medical Dictionary for Regulatory Activities (MedDRA.)
Time Frame From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
54.2 56.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.726
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
22.Secondary Outcome
Title Percentage of Participants With Angioedema
Hide Description Includes treatment-emergent adverse events based on categorization by the investigator as angioedema, regardless of the event preferred term in MedDRA.
Time Frame From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
1.3 1.4
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1.000
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
23.Secondary Outcome
Title Percentage of Participants With Malignancy
Hide Description Includes treatment-emergent adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferredterm in MedDRA.
Time Frame From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
3.9 2.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.753
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
24.Secondary Outcome
Title Percentage of Participants With Hyperkalemia
Hide Description Hyperkalemia defined as serum potassium >5.6 millimoles per liter (mmol/L)
Time Frame Baseline, Pre-SRL (from first dose of ramipril/placebo up to SRL conversion), On-Therapy (up to 52 weeks after SRL conversion), and Off-Therapy Period (up to 56 weeks after SRL conversion)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population; n=number of participants assessed for the specified parameter at a given visit.
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description:
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Overall Number of Participants Analyzed 155 140
Measure Type: Number
Unit of Measure: percentage of participants
Baseline (n=155,140) 0.0 1.4
Pre-SRL (n=151,135) 4.6 1.5
On-Therapy (n=138,124) 0.7 1.6
Off-Therapy (n=34,36) 2.9 0.0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.224
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Pre-SRL
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.179
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments On-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.604
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ramipril, Placebo
Comments Off-Therapy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.486
Comments 2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
Method Fisher Exact
Comments [Not Specified]
Time Frame Randomization through Week 52 following conversion to SRL
Adverse Event Reporting Description The same event may appear as both an adverse event (AE) and a serious AE (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as nonserious in another participant, or one participant may have experienced both a serious and nonserious event during the study.
 
Arm/Group Title Ramipril Placebo
Hide Arm/Group Description Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study. Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
All-Cause Mortality
Ramipril Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ramipril Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   50/155 (32.26%)   39/140 (27.86%) 
Blood and lymphatic system disorders     
Anaemia * 1  2/155 (1.29%)  0/140 (0.00%) 
Iron deficiency anaemia * 1  0/155 (0.00%)  1/140 (0.71%) 
Leukocytosis * 1  0/155 (0.00%)  1/140 (0.71%) 
Cardiac disorders     
Atrial fibrillation * 1  1/155 (0.65%)  0/140 (0.00%) 
Palpitations * 1  0/155 (0.00%)  1/140 (0.71%) 
Ventricular tachycardia * 1  0/155 (0.00%)  1/140 (0.71%) 
Congenital, familial and genetic disorders     
Congenital cystic kidney disease * 1  1/155 (0.65%)  0/140 (0.00%) 
Gastrointestinal disorders     
Colitis * 1  0/155 (0.00%)  1/140 (0.71%) 
Colitis ulcerative * 1  0/155 (0.00%)  1/140 (0.71%) 
Diarrhoea * 1  4/155 (2.58%)  2/140 (1.43%) 
Ileus * 1  1/155 (0.65%)  0/140 (0.00%) 
Inguinal hernia * 1  1/155 (0.65%)  0/140 (0.00%) 
Mouth ulceration * 1  1/155 (0.65%)  1/140 (0.71%) 
Nausea * 1  1/155 (0.65%)  0/140 (0.00%) 
Small intestinal obstruction * 1  0/155 (0.00%)  1/140 (0.71%) 
Umbilical hernia * 1  0/155 (0.00%)  1/140 (0.71%) 
Vomiting * 1  3/155 (1.94%)  0/140 (0.00%) 
General disorders     
Chest pain * 1  0/155 (0.00%)  1/140 (0.71%) 
Generalised oedema * 1  1/155 (0.65%)  0/140 (0.00%) 
Impaired healing * 1  0/155 (0.00%)  1/140 (0.71%) 
Oedema peripheral * 1  1/155 (0.65%)  0/140 (0.00%) 
Pyrexia * 1  4/155 (2.58%)  0/140 (0.00%) 
Hepatobiliary disorders     
Cholecystitis acute * 1  1/155 (0.65%)  0/140 (0.00%) 
Immune system disorders     
Kidney transplant rejection * 1  3/155 (1.94%)  3/140 (2.14%) 
Transplant rejection * 1  11/155 (7.10%)  1/140 (0.71%) 
Infections and infestations     
Cellulitis * 1  4/155 (2.58%)  1/140 (0.71%) 
Cytomegalovirus infection * 1  1/155 (0.65%)  0/140 (0.00%) 
Cytomegalovirus viraemia * 1  0/155 (0.00%)  1/140 (0.71%) 
Diabetic foot infection * 1  1/155 (0.65%)  0/140 (0.00%) 
Diverticulitis * 1  0/155 (0.00%)  1/140 (0.71%) 
Gastroenteritis * 1  2/155 (1.29%)  1/140 (0.71%) 
Gastroenteritis viral * 1  1/155 (0.65%)  1/140 (0.71%) 
H1N1 influenza * 1  1/155 (0.65%)  1/140 (0.71%) 
Herpes zoster * 1  0/155 (0.00%)  1/140 (0.71%) 
Herpes zoster disseminated * 1  1/155 (0.65%)  0/140 (0.00%) 
Infected skin ulcer * 1  0/155 (0.00%)  1/140 (0.71%) 
Influenza * 1  1/155 (0.65%)  0/140 (0.00%) 
Oral bacterial infection * 1  1/155 (0.65%)  0/140 (0.00%) 
Oral infection * 1  1/155 (0.65%)  0/140 (0.00%) 
Pharyngitis streptococcal * 1  0/155 (0.00%)  1/140 (0.71%) 
Pneumonia * 1  2/155 (1.29%)  0/140 (0.00%) 
Pulmonary sepsis * 1  0/155 (0.00%)  1/140 (0.71%) 
Pyelonephritis acute * 1  1/155 (0.65%)  1/140 (0.71%) 
Sepsis * 1  0/155 (0.00%)  1/140 (0.71%) 
Sinusitis * 1  0/155 (0.00%)  1/140 (0.71%) 
Urinary tract infection * 1  3/155 (1.94%)  1/140 (0.71%) 
Viral infection * 1  1/155 (0.65%)  1/140 (0.71%) 
Viral upper respiratory tract infection * 1  1/155 (0.65%)  0/140 (0.00%) 
Injury, poisoning and procedural complications     
Complications of transplanted kidney * 1  1/155 (0.65%)  1/140 (0.71%) 
Graft complication * 1  1/155 (0.65%)  0/140 (0.00%) 
Ligament rupture * 1