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

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00502242
• Collaborator: (none)
• Enrollment: 229
• Locations: 50
• Arms: 2
• Duration (Months): 69
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of the study is to determine the efficacy of ramipril in preventing a urinary protein to creatinine ratio (U p/c) greater than 0.5 following conversion to sirolimus from a calcineurin inhibitor (CNI) in maintenance kidney transplant patients.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplant	Drug: ramipril; Drug: ramipril	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 229 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Dec 1, 2007
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: A Capsule - initial treatment is 5 mg (active)- oral - once per day	Drug: ramipril; Capsule - initial treatment is 5 mg (active)- oral - once per day
Placebo Comparator: B Capsule - initial treatment is 5 mg (placebo) - oral - once per day	Drug: ramipril; Capsule - initial treatment is 5 mg (placebo) - oral - once per day

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL [From Day 1 of SRL conversion to 52 weeks after conversion]

   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.

Secondary Outcome Measures

1. Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL [From Day 1 of SRL conversion to 52 weeks after conversion]

   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.

2. Percentage of Participants With U p/c <0.5 at 24 and 52 Weeks Following Conversion to Sirolimus [24 weeks and 52 weeks after conversion]

   Spot urine sample of protein and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.

3. Percentage of Participants With Urinary Albumin to Creatinine Ratio (U Alb/c) <0.5 at 24 and 52 Weeks Following Conversion to SRL [24 weeks and 52 weeks after conversion]

   Spot urine sample of albumin and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.

4. 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 [24 weeks and 52 weeks after conversion]

   The U alb/c and U p/c must have been collected on the same day to be counted as the numerator.

5. U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL [Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion]

   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.

6. U Alb/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL [Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion]

   U alb/c was measured in mg/mg. Baseline U alb/c values were the last values of the pre-SRL conversion period.

7. Percentage of Participants Who Discontinued SRL Therapy at 24 and 52 Weeks Following Conversion to SRL [24 weeks and 52 weeks after conversion]

   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).

8. Abbreviated Modified Diet in Renal Disease (MDRD) Glomerular Filtration Rate (GFR) at Weeks 12, 24, and 52 Following Conversion to SRL [12, 24, and 52 weeks following conversion]

   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.

9. Fraction of Albumin (Milligrams Per Deciliter [mg/dL]) to Protein (mg/dL) in Urine at 24 and 52 Weeks After Conversion to SRL [24 weeks and 52 weeks after conversion]

   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.

10. Percentage of Participants With Potentially Clinically Important Blood Pressure (BP) Values by Diastolic and Systolic BP Category [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)]

    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.

11. SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval [From Day 1 of SRL conversion to 52 weeks after conversion]

    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.

12. Percentage of Participants With Hemoglobin Levels ≤100 Grams Per Liter (g/L) [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)]

13. Percentage of Participants Using Red Blood Cell Production Stimulants (Erythropoiesis Stimulating Agents [ESAs]) [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)]

14. Change From Baseline in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) at 4, 12, 24, and 52 Weeks Following Conversion to SRL [4, 12, 24, and 52 weeks after conversion]

    Parameters assessed included (all fasting) total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-densitylipoprotein cholesterol (HDL-C).

15. Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event [From Day 1 of SRL conversion to 52 weeks after conversion]

    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.

16. Percentage of Participants With First BCAR at 24 and 52 Weeks Following Conversion to SRL [24 weeks and 52 weeks after conversion]

    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.

17. Number of Participants With BCAR by Severity of First BCAR [From Day 1 of SRL conversion to 52 weeks after conversion]

    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.

18. Percentage of Participants With Graft Loss at 24 and 52 Weeks Following Conversion to SRL [24 weeks and 52 weeks after conversion]

    Graft loss was defined as physical loss (nephrectomy orretransplantation), functional loss (requiring dialysis for ≥56days with no return of graft function), or death.

19. Percentage of Participants Using Statins [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)]

20. Percentage of Participants With an Infection [From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion]

    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.)

21. Percentage of Participants With Angioedema [From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion]

    Includes treatment-emergent adverse events based on categorization by the investigator as angioedema, regardless of the event preferred term in MedDRA.

22. Percentage of Participants With Malignancy [From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion]

    Includes treatment-emergent adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferredterm in MedDRA.

23. Percentage of Participants With Hyperkalemia [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)]

    Hyperkalemia defined as serum potassium >5.6 millimoles per liter (mmol/L)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Receiving cyclosporine (CsA) or tacrolimus (TAC) since the first month post-transplant.

• In addition to a calcineurin inhibitor (CNI), subjects must be treated with either corticosteroids at a dosage range of 2.5 to 15 mg/day for prednisone or prednisolone (2 to 12mg/day for methylprednisolone or the alternate day equivalent) or a steroid-free regimen for a minimum of 12 weeks before randomization or either MMF (>/=500mg/day), mycophenolate sodium (MPS) (>/=360 mg/day) or AZA (>/=50mg/day). Subjects must be taking a minimum of 2 immunosuppressive drugs if on a steroid-free regimen.

• Subject is 3 to 60 months after renal transplantation.

• Subject is greater than 12 weeks after treatment for any acute rejection.

Exclusion Criteria:

• Subjects who are currently receiving, or have received within 4 weeks before enrollment, RAAS blockade.

• Subjects with a calculated GFR < 40mL/min (per the Modification of Diet in Renal Disease [MDRD-7] or abbreviated MDRD formula).

• Subjects with a urine protein to creatinine ratio (U p/c) of >0.3.

• Subjects with a history of uncontrolled systolic blood pressure (SBP >140 mm Hg).

• Subjects with severe hepatic impairment (Grade C Child-Pugh score). Additional Inclusion / Exclusion Criteria apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Los Angeles	California	United States	90033-4612
2	Pfizer Investigational Site	Los Angeles	California	United States	90033
3	Pfizer Investigational Site	San Francisco	California	United States	94115
4	Pfizer Investigational Site	Aurora	Colorado	United States	80045
5	Pfizer Investigational Site	Denver	Colorado	United States	80218
6	Pfizer Investigational Site	Gainesville	Florida	United States	32610
7	Pfizer Investigational Site	Chicago	Illinois	United States	60637
8	Pfizer Investigational Site	Iowa City	Iowa	United States	52242
9	Pfizer Investigational Site	Lexington	Kentucky	United States	40536-0293
10	Pfizer Investigational Site	Portland	Maine	United States	04102
11	Pfizer Investigational Site	Boston	Massachusetts	United States	02215
12	Pfizer Investigational Site	Springfield	Massachusetts	United States	01107
13	Pfizer Investigational Site	Springfield	Massachusetts	United States	01199
14	Pfizer Investigational Site	Gosse Pointe	Michigan	United States	48236
15	Pfizer Investigational Site	Buffalo	New York	United States	14215
16	Pfizer Investigational Site	Valhalla	New York	United States	10595
17	Pfizer Investigational Site	Cleveland	Ohio	United States	44106
18	Pfizer Investigational Site	Cleveland	Ohio	United States	44195
19	Pfizer Investigational Site	Harrisburg	Pennsylvania	United States	17104
20	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19102-1192
21	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19102
22	Pfizer Investigational Site	Philadelphia	Pennsylvania	United States	19107
23	Pfizer Investigational Site	Providence	Rhode Island	United States	02903
24	Pfizer Investigational Site	Charleston	South Carolina	United States	29425-6290
25	Pfizer Investigational Site	Capital Federal	Buenos Aires	Argentina	1425
26	Pfizer Investigational Site	San Martin	Buenos Aires	Argentina	1650 CP
27	Pfizer Investigational Site	Buenos Aires		Argentina	1181
28	Pfizer Investigational Site	Cordoba		Argentina	5016
29	Pfizer Investigational Site	Córdoba		Argentina	5016
30	Pfizer Investigational Site	Brisbane	Queensland	Australia	4029
31	Pfizer Investigational Site	North Terrace		Australia	5000
32	Pfizer Investigational Site	Woodville South		Australia	SA 5011
33	Pfizer Investigational Site	Linz		Austria	4020
34	Pfizer Investigational Site	Rio de Janeiro	RJ	Brazil	21041-030
35	Pfizer Investigational Site	Porto Alegre	RS	Brazil	90020-090
36	Pfizer Investigational Site	Porto Alegre	RS	Brazil	90035-074
37	Pfizer Investigational Site	Sao Paulo	SP	Brazil	01323-001
38	Pfizer Investigational Site	Sao Paulo	SP	Brazil	01323-030
39	Pfizer Investigational Site	Sao Paulo	SP	Brazil	04038-002
40	Pfizer Investigational Site	Sao Paulo	SP	Brazil	04039-033
41	Pfizer Investigational Site	Montreal	Quebec	Canada	H2L 4M1
42	Pfizer Investigational Site	Erlangen		Germany	91054
43	Pfizer Investigational Site	Szeged		Hungary	6720
44	Pfizer Investigational Site	Petach Tikva		Israel	49100
45	Pfizer Investigational Site	Mexico City		Mexico	14000
46	Pfizer Investigational Site	Veracruz		Mexico	91700
47	Pfizer Investigational Site	Szczecin		Poland	70-111
48	Pfizer Investigational Site	Johannesburg	Gauteng	South Africa	2193
49	Pfizer Investigational Site	Cape Town	Western Cape	South Africa	7925
50	Pfizer Investigational Site	Cape Town	Western Cape	South Africa	8001

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT00502242
• Other Study ID Numbers: 0468E5-4439; B1741001
• First Posted: Jul 17, 2007
• Last Update Posted: Aug 27, 2014
• Last Verified: Aug 1, 2014

• Additional relevant MeSH terms: Ramipril

Study Results

Participant Flow

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 Detail	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
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

Baseline Characteristics

Arm/Group Title	Ramipril	Placebo	Total
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 Participants	155	140	295
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.8 (12.7)	47.5 (12.9)	47.1 (12.8)
Sex: Female, Male (Count of Participants)
Female	48 31%	50 35.7%	98 33.2%
Male	107 69%	90 64.3%	197 66.8%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL
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

Outcome Measure Data

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
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.
Measure Participants	138	126
Number (95% Confidence Interval) [percentage of participants]	6.2 4%	23.2 16.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
Number (95% Confidence Interval) [percentage of participants]	14.4 9.3%	29.2 20.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

Analysis Population Description

mITT population; includes assessments from On-Therapy and Off-Therapy Periods.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
Up to 24 weeks post-conversion	92.0 59.4%	77.8 55.6%
Up to 52 weeks post-conversion	82.6 53.3%	73.0 52.1%

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
Statistical Test of Hypothesis	p-Value	0.002
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.074
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
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

Outcome Measure Data

Analysis Population Description

mITT population; includes assessments from On-Therapy and Off-Therapy Periods.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
Up to 24 weeks post-conversion	95.7 61.7%	89.7 64.1%
Up to 52 weeks post-conversion	88.4 57%	82.5 58.9%

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
Statistical Test of Hypothesis	p-Value	0.093
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.219
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
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

Outcome Measure Data

Analysis Population Description

mITT population; includes assessments from On-Therapy and Off-Therapy Periods.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
Up to 24 weeks post-conversion	91.3 58.9%	77.0 55%
Up to 52 weeks post-conversion	79.0 51%	70.6 50.4%

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
Statistical Test of Hypothesis	p-Value	0.002
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.121
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
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

Outcome Measure Data

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
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.
Measure Participants	138	126
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)

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.16
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.36
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.18
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.52
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.61
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.34
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.63
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.48
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.78
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.43
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.82
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.40
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.67
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.56
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.86
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

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
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.
Measure Participants	138	126
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)

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.46
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.05
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.43
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.37
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.67
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.74
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	1.91
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.92
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.33
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	3.39
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.50
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	3.39
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.52
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	3.27
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean fold-change.

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	2.92
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Adjusted Geometric Mean Fold Change
	Estimated Value	3.45
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Adjusted for baseline

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
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
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
Up to 24 weeks post-conversion	15.2 9.8%	15.9 11.4%
Up to 52 weeks post-conversion	19.6 12.6%	28.6 20.4%

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
Statistical Test of Hypothesis	p-Value	1.0000
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.1115
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
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

Outcome Measure Data

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
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.
Measure Participants	138	126
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)

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
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

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
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

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
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
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

Outcome Measure Data

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
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.
Measure Participants	111	110
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Week 24
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	Estimation Comments	Treatment ratio (Ramipril/Placebo) in the geometric mean.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
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
	Parameter Dispersion	Type: Value:
	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
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)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Baseline, Low DBP ≤50 mmHg (n=155,140)	0.0 0%	0.7 0.5%
Baseline, Low SBP: ≤90 mmHg (n=155,140)	0.0 0%	0.7 0.5%
Pre-SRL, Low DBP: ≤50 mmHg (n=152,135)	0.0 0%	0.7 0.5%
Pre-SRL, High DBP: ≥110 mmHg (n=152,135)	0.0 0%	1.5 1.1%
Pre-SRL, Low SBP: ≤90 mmHg (n=152,135)	0.0 0%	0.7 0.5%
Pre-SRL, High SBP: ≥180 mmHg (n=152,135)	0.7 0.5%	0.7 0.5%
On Therapy, Low DBP: ≤50 mmHg (n=138,126)	3.6 2.3%	2.4 1.7%
On Therapy, High DBP: ≥110 mmHg (n=138,126)	0.0 0%	1.6 1.1%
On Therapy, Low SBP: ≤90 mmHg (n=138,126)	3.6 2.3%	4.0 2.9%
On Therapy, High SBP: ≥180 mmHg (n=138,126)	0.7 0.5%	4.0 2.9%
Off Therapy, High DBP ≥110 mmHg (n=35,69)	2.9 1.9%	1.4 1%
Off Therapy, Low SBP: ≤90 mmHg (n=35,69)	2.9 1.9%	1.4 1%

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
Statistical Test of Hypothesis	p-Value	0.470
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.220
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.470
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	1.000
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.725
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.227
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	1.000
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.106
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	1.000
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	1.000
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.475
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
Statistical Test of Hypothesis	p-Value	0.475
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

12. Secondary Outcome

Title	SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval
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

Outcome Measure Data

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
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.
Measure Participants	258
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)
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)

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Baseline (n=155,140)	1.3 0.8%	1.4 1%
Pre-SRL (n=148,129)	2.0 1.3%	0.8 0.6%
On-Therapy (n=138,124)	17.4 11.2%	12.1 8.6%
Off-Therapy (n=33,34)	9.1 5.9%	2.9 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Pre-SRL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.626
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	On-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Off-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.356
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

14. Secondary Outcome

Title	Percentage of Participants Using Red Blood Cell Production Stimulants (Erythropoiesis Stimulating Agents [ESAs])
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)

Outcome Measure Data

Analysis Population Description

Safety population; n=number of participants analyzed for the specified parameter at a given visit.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Baseline (n=155,140)	5.8 3.7%	1.4 1%
Pre-SRL (n=155,140)	4.5 2.9%	0.7 0.5%
On-Therapy (n=138,126)	4.3 2.8%	3.2 2.3%
Off-Therapy (n=136,122)	1.5 1%	4.1 2.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.064
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Pre-SRL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	On-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.752
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Off-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.261
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

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
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

Outcome Measure Data

Analysis Population Description

Safety population; n=number of participants assessed for the specified parameter at a given visit.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	128	109
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)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	TC, Week 4
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	TC, Week 12
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	TC, Week 24
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	TC, Week 52
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	HDL-C, Week 4
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	HDL-C, Week 12
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	HDL-C, Week 24
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	HDL-C, Week 52
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	LDL-C, Week 4
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	LDL-C, Week 12
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	LDL-C, Week 24
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	LDL-C, Week 52
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Triglycerides, Week 4
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Triglycerides, Week 12
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Triglycerides, Week 24
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Triglycerides, Week 52
	Type of Statistical Test	Superiority or Other
	Comments
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
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.17
	Estimation Comments

16. Secondary Outcome

Title	Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event
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

Outcome Measure Data

Analysis Population Description

mITT population; includes BCAR occurring in On-Therapy and Off-Therapy Periods.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
Number [participants]	13 8.4%	5 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0732
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	2.487
	Confidence Interval	(2-Sided) 95%; 0.887 to 6.978
	Parameter Dispersion	Type: Value:
	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
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

Outcome Measure Data

Analysis Population Description

mITT population; includes BCAR occurring in the On-Therapy and Off-Therapy Periods

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
24 weeks post-conversion	8.0 5.2%	0.8 0.6%
52 weeks post-conversion	9.5 6.1%	3.2 2.3%

18. Secondary Outcome

Title	Number of Participants With BCAR by Severity of First BCAR
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

Outcome Measure Data

Analysis Population Description

mITT population; only participants with BCAR were included in the anlaysis.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	13	8
Post-SRL, AM BCAR, Grade I (mild)	1 0.6%	2 1.4%
Post-SRL, AM BCAR, Grade II (mod)	0 0%	1 0.7%
Post-SRL, AM BCAR, Grade III (severe)	0 0%	1 0.7%
Post-SRL, T-Cell BCAR, Grade I (mild)	12 7.7%	4 2.9%
Post-SRL (On-Therapy), AM BCAR, Grade I (mild)	1 0.6%	1 0.7%
Post-SRL (On-Therapy), AM BCAR, Grade II (mod)	0 0%	1 0.7%
Post-SRL (On-Therapy), T-Cell BCAR, Grade I (mild)	10 6.5%	3 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Post-SRL, AM BCAR
	Type of Statistical Test	Superiority or Other
	Comments
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

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
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
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

Outcome Measure Data

Analysis Population Description

mITT population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	138	126
Week 24	0.0 0%	0.0 0%
Week 52	0.0 0%	0.8 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Week 52
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4773
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

20. Secondary Outcome

Title	Percentage of Participants Using Statins
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)

Outcome Measure Data

Analysis Population Description

Safety population; n=number of participants analyzed for the specified parameter at a given visit.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Baseline (n=155,140)	45.8 29.5%	36.4 26%
Pre-SRL (n=155,140)	45.2 29.2%	40.0 28.6%
On-Therapy (n=138,126)	67.4 43.5%	72.2 51.6%
Off-Therapy (n=136,122)	62.5 40.3%	68.9 49.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.124
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Pre-SRL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.410
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	On-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.423
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Off-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

21. Secondary Outcome

Title	Percentage of Participants With an Infection
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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Number [percentage of participants]	54.2 35%	56.4 40.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.726
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

22. Secondary Outcome

Title	Percentage of Participants With Angioedema
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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Number [percentage of participants]	1.3 0.8%	1.4 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

23. Secondary Outcome

Title	Percentage of Participants With Malignancy
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

Outcome Measure Data

Analysis Population Description

Safety population

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Number [percentage of participants]	3.9 2.5%	2.9 2.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.753
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

24. Secondary Outcome

Title	Percentage of Participants With Hyperkalemia
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)

Outcome Measure Data

Analysis Population Description

Safety population; n=number of participants assessed for the specified parameter at a given visit.

Arm/Group Title	Ramipril	Placebo
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.
Measure Participants	155	140
Baseline (n=155,140)	0.0 0%	1.4 1%
Pre-SRL (n=151,135)	4.6 3%	1.5 1.1%
On-Therapy (n=138,124)	0.7 0.5%	1.6 1.1%
Off-Therapy (n=34,36)	2.9 1.9%	0.0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Baseline
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Pre-SRL
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.179
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	On-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.604
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Ramipril, Placebo
	Comments	Off-Therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.486
	Comments	2-sided p-value; alpha=0.05 (unadjusted for multiplicity)
	Method	Fisher Exact
	Comments

Adverse Events

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
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 (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Ramipril		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/155 (32.3%)		39/140 (27.9%)
Blood and lymphatic system disorders
Anaemia	2/155 (1.3%)		0/140 (0%)
Iron deficiency anaemia	0/155 (0%)		1/140 (0.7%)
Leukocytosis	0/155 (0%)		1/140 (0.7%)
Cardiac disorders
Atrial fibrillation	1/155 (0.6%)		0/140 (0%)
Palpitations	0/155 (0%)		1/140 (0.7%)
Ventricular tachycardia	0/155 (0%)		1/140 (0.7%)
Congenital, familial and genetic disorders
Congenital cystic kidney disease	1/155 (0.6%)		0/140 (0%)
Gastrointestinal disorders
Colitis	0/155 (0%)		1/140 (0.7%)
Colitis ulcerative	0/155 (0%)		1/140 (0.7%)
Diarrhoea	4/155 (2.6%)		2/140 (1.4%)
Ileus	1/155 (0.6%)		0/140 (0%)
Inguinal hernia	1/155 (0.6%)		0/140 (0%)
Mouth ulceration	1/155 (0.6%)		1/140 (0.7%)
Nausea	1/155 (0.6%)		0/140 (0%)
Small intestinal obstruction	0/155 (0%)		1/140 (0.7%)
Umbilical hernia	0/155 (0%)		1/140 (0.7%)
Vomiting	3/155 (1.9%)		0/140 (0%)
General disorders
Chest pain	0/155 (0%)		1/140 (0.7%)
Generalised oedema	1/155 (0.6%)		0/140 (0%)
Impaired healing	0/155 (0%)		1/140 (0.7%)
Oedema peripheral	1/155 (0.6%)		0/140 (0%)
Pyrexia	4/155 (2.6%)		0/140 (0%)
Hepatobiliary disorders
Cholecystitis acute	1/155 (0.6%)		0/140 (0%)
Immune system disorders
Kidney transplant rejection	3/155 (1.9%)		3/140 (2.1%)
Transplant rejection	11/155 (7.1%)		1/140 (0.7%)
Infections and infestations
Cellulitis	4/155 (2.6%)		1/140 (0.7%)
Cytomegalovirus infection	1/155 (0.6%)		0/140 (0%)
Cytomegalovirus viraemia	0/155 (0%)		1/140 (0.7%)
Diabetic foot infection	1/155 (0.6%)		0/140 (0%)
Diverticulitis	0/155 (0%)		1/140 (0.7%)
Gastroenteritis	2/155 (1.3%)		1/140 (0.7%)
Gastroenteritis viral	1/155 (0.6%)		1/140 (0.7%)
H1N1 influenza	1/155 (0.6%)		1/140 (0.7%)
Herpes zoster	0/155 (0%)		1/140 (0.7%)
Herpes zoster disseminated	1/155 (0.6%)		0/140 (0%)
Infected skin ulcer	0/155 (0%)		1/140 (0.7%)
Influenza	1/155 (0.6%)		0/140 (0%)
Oral bacterial infection	1/155 (0.6%)		0/140 (0%)
Oral infection	1/155 (0.6%)		0/140 (0%)
Pharyngitis streptococcal	0/155 (0%)		1/140 (0.7%)
Pneumonia	2/155 (1.3%)		0/140 (0%)
Pulmonary sepsis	0/155 (0%)		1/140 (0.7%)
Pyelonephritis acute	1/155 (0.6%)		1/140 (0.7%)
Sepsis	0/155 (0%)		1/140 (0.7%)
Sinusitis	0/155 (0%)		1/140 (0.7%)
Urinary tract infection	3/155 (1.9%)		1/140 (0.7%)
Viral infection	1/155 (0.6%)		1/140 (0.7%)
Viral upper respiratory tract infection	1/155 (0.6%)		0/140 (0%)
Injury, poisoning and procedural complications
Complications of transplanted kidney	1/155 (0.6%)		1/140 (0.7%)
Graft complication	1/155 (0.6%)		0/140 (0%)
Ligament rupture	0/155 (0%)		1/140 (0.7%)
Limb traumatic amputation	0/155 (0%)		1/140 (0.7%)
Medication error	1/155 (0.6%)		0/140 (0%)
Meniscus injury	0/155 (0%)		1/140 (0.7%)
Overdose	0/155 (0%)		1/140 (0.7%)
Investigations
Blood creatinine increased	2/155 (1.3%)		1/140 (0.7%)
Blood urea increased	1/155 (0.6%)		0/140 (0%)
Clostridium test positive	0/155 (0%)		1/140 (0.7%)
Cytomegalovirus test positive	1/155 (0.6%)		0/140 (0%)
Immunosuppressant drug level increased	0/155 (0%)		1/140 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	3/155 (1.9%)		2/140 (1.4%)
Haemangioblastoma	1/155 (0.6%)		0/140 (0%)
Squamous cell carcinoma	3/155 (1.9%)		1/140 (0.7%)
Squamous cell carcinoma of skin	0/155 (0%)		1/140 (0.7%)
Nervous system disorders
Cerebral infarction	0/155 (0%)		1/140 (0.7%)
Cerebrovascular accident	0/155 (0%)		1/140 (0.7%)
Encephalitis	1/155 (0.6%)		0/140 (0%)
Headache	3/155 (1.9%)		0/140 (0%)
Syncope	2/155 (1.3%)		0/140 (0%)
Renal and urinary disorders
Obstructive uropathy	1/155 (0.6%)		0/140 (0%)
Renal cyst ruptured	0/155 (0%)		1/140 (0.7%)
Renal impairment	1/155 (0.6%)		0/140 (0%)
Ureteric obstruction	0/155 (0%)		1/140 (0.7%)
Urinary retention	1/155 (0.6%)		0/140 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/155 (0%)		1/140 (0.7%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/155 (0%)		1/140 (0.7%)
Cough	1/155 (0.6%)		0/140 (0%)
Dyspnoea	0/155 (0%)		1/140 (0.7%)
Dyspnoea exertional	1/155 (0.6%)		0/140 (0%)
Pneumonitis	2/155 (1.3%)		0/140 (0%)
Skin and subcutaneous tissue disorders
Angioedema	1/155 (0.6%)		1/140 (0.7%)
Dermal cyst	0/155 (0%)		1/140 (0.7%)
Diabetic foot	1/155 (0.6%)		0/140 (0%)
Skin ulcer	0/155 (0%)		1/140 (0.7%)
Vascular disorders
Deep vein thrombosis	1/155 (0.6%)		2/140 (1.4%)
Embolism	0/155 (0%)		1/140 (0.7%)
Peripheral vascular disorder	0/155 (0%)		1/140 (0.7%)
Superior vena caval stenosis	0/155 (0%)		1/140 (0.7%)
Other (Not Including Serious) Adverse Events
	Ramipril		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/155 (86.5%)		123/140 (87.9%)
Blood and lymphatic system disorders
Anaemia	18/155 (11.6%)		10/140 (7.1%)
Leukopenia	19/155 (12.3%)		6/140 (4.3%)
Thrombocytopenia	5/155 (3.2%)		7/140 (5%)
Gastrointestinal disorders
Aphthous stomatitis	12/155 (7.7%)		14/140 (10%)
Diarrhoea	40/155 (25.8%)		37/140 (26.4%)
Mouth ulceration	12/155 (7.7%)		17/140 (12.1%)
Nausea	8/155 (5.2%)		9/140 (6.4%)
Stomatitis	7/155 (4.5%)		11/140 (7.9%)
Vomiting	10/155 (6.5%)		8/140 (5.7%)
General disorders
Fatigue	12/155 (7.7%)		7/140 (5%)
Local swelling	3/155 (1.9%)		9/140 (6.4%)
Oedema peripheral	27/155 (17.4%)		30/140 (21.4%)
Pyrexia	11/155 (7.1%)		9/140 (6.4%)
Infections and infestations
Bronchitis	4/155 (2.6%)		7/140 (5%)
Nasopharyngitis	8/155 (5.2%)		7/140 (5%)
Upper respiratory tract infection	27/155 (17.4%)		16/140 (11.4%)
Urinary tract infection	12/155 (7.7%)		13/140 (9.3%)
Investigations
Blood creatinine increased	24/155 (15.5%)		11/140 (7.9%)
Weight increased	8/155 (5.2%)		5/140 (3.6%)
Metabolism and nutrition disorders
Dyslipidaemia	14/155 (9%)		19/140 (13.6%)
Hypercholesterolaemia	17/155 (11%)		14/140 (10%)
Hyperlipidaemia	15/155 (9.7%)		9/140 (6.4%)
Hypertriglyceridaemia	16/155 (10.3%)		15/140 (10.7%)
Hypokalaemia	3/155 (1.9%)		9/140 (6.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	15/155 (9.7%)		13/140 (9.3%)
Back pain	10/155 (6.5%)		6/140 (4.3%)
Pain in extremity	6/155 (3.9%)		12/140 (8.6%)
Nervous system disorders
Dizziness	12/155 (7.7%)		10/140 (7.1%)
Headache	19/155 (12.3%)		16/140 (11.4%)
Renal and urinary disorders
Proteinuria	8/155 (5.2%)		15/140 (10.7%)
Respiratory, thoracic and mediastinal disorders
Cough	24/155 (15.5%)		14/140 (10%)
Oropharyngeal pain	7/155 (4.5%)		12/140 (8.6%)
Skin and subcutaneous tissue disorders
Acne	18/155 (11.6%)		25/140 (17.9%)
Rash	5/155 (3.2%)		13/140 (9.3%)
Vascular disorders
Hypertension	10/155 (6.5%)		14/140 (10%)
Hypotension	14/155 (9%)		7/140 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.