Phase 4
N=295
Study Evaluating The Effect Of Ramipril On Urinary Protein Excretion In Renal Transplant Patients Converted To Sirolimus
Kidney Transplant
Bottom Line
View on ClinicalTrials.gov: NCT00502242 ↗Enrolled (actual)
295
Serious AEs
30.2%
Results posted
Aug 2014
Primary outcome: Primary: Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL — 6.2; 23.2 percentage of participants — p=0.0002
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- ramipril (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Pfizer
- Primary completion
- Sep 2013
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL |
6.2; 23.2 | 0.0002 sig |
| SECONDARY Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL |
14.4; 29.2 | 0.0031 sig |
| SECONDARY Percentage of Participants With U p/c <0.5 at 24 and 52 Weeks Following Conversion to Sirolimus |
92.0; 77.8; 82.6; 73.0 | 0.002 sig |
| SECONDARY Percentage of Participants With Urinary Albumin to Creatinine Ratio (U Alb/c) <0.5 at 24 and 52 Weeks Following Conversion to SRL |
95.7; 89.7; 88.4; 82.5 | 0.093 |
| SECONDARY 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 |
91.3; 77.0; 79.0; 70.6 | 0.002 sig |
| SECONDARY U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL |
0.17; 0.15; 0.18; 0.23; 0.18; 0.28 | 0.0098 sig |
| SECONDARY U Alb/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL |
0.04; 0.02; 0.03; 0.06; 0.03; 0.09 | 0.0034 sig |
| SECONDARY Percentage of Participants Who Discontinued SRL Therapy at 24 and 52 Weeks Following Conversion to SRL |
15.2; 15.9; 19.6; 28.6 | 1.0000 |
| SECONDARY Abbreviated Modified Diet in Renal Disease (MDRD) Glomerular Filtration Rate (GFR) at Weeks 12, 24, and 52 Following Conversion to SRL |
62.06; 63.30; 64.91; 66.58; 65.18; 63.85 | 0.4933 |
| SECONDARY Fraction of Albumin (Milligrams Per Deciliter [mg/dL]) to Protein (mg/dL) in Urine at 24 and 52 Weeks After Conversion to SRL |
0.19; 0.25; 0.22; 0.25 | 0.1167 |
| SECONDARY Percentage of Participants With Potentially Clinically Important Blood Pressure (BP) Values by Diastolic and Systolic BP Category |
0.0; 0.7; 0.0; 0.7; 0.0; 0.7 | 0.470 |
| SECONDARY SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval |
9.853; 9.872; 9.273; 9.274; 9.316; 8.961 | — |
| SECONDARY Percentage of Participants With Hemoglobin Levels ≤100 Grams Per Liter (g/L) |
1.3; 1.4; 2.0; 0.8; 17.4; 12.1 | 1.000 |
| SECONDARY Percentage of Participants Using Red Blood Cell Production Stimulants (Erythropoiesis Stimulating Agents [ESAs]) |
5.8; 1.4; 4.5; 0.7; 4.3; 3.2 | 0.064 |
| SECONDARY Change From Baseline in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) at 4, 12, 24, and 52 Weeks Following Conversion to SRL |
0.83; 0.91; 0.94; 0.92; 0.91; 0.87 | 0.381 |
| SECONDARY Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event |
13; 5 | 0.0732 |
| SECONDARY Percentage of Participants With First BCAR at 24 and 52 Weeks Following Conversion to SRL |
8.0; 0.8; 9.5; 3.2 | — |
| SECONDARY Number of Participants With BCAR by Severity of First BCAR |
1; 2; 0; 1; 0; 1 | 0.7165 |
| SECONDARY Percentage of Participants With Graft Loss at 24 and 52 Weeks Following Conversion to SRL |
0.0; 0.0; 0.0; 0.8 | 0.4773 |
| SECONDARY Percentage of Participants Using Statins |
45.8; 36.4; 45.2; 40.0; 67.4; 72.2 | 0.124 |
| SECONDARY Percentage of Participants With an Infection |
54.2; 56.4 | 0.726 |
| SECONDARY Percentage of Participants With Angioedema |
1.3; 1.4 | 1.000 |
| SECONDARY Percentage of Participants With Malignancy |
3.9; 2.9 | 0.753 |
| SECONDARY Percentage of Participants With Hyperkalemia |
0.0; 1.4; 4.6; 1.5; 0.7; 1.6 | 0.224 |
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.
Eligibility Criteria
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 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.
Data sourced from ClinicalTrials.gov (NCT00502242). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.