A Phase 4 interventional study of ramipril and ramipril in Kidney Transplant, sponsored by Pfizer. Completed at 50 sites in 12 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-08-27.
Sponsored by Pfizer · Phase 4, Interventional, and Treatment
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.
Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.
Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Capsule - initial treatment is 5 mg (active)- oral - once per day
Drug: ramipril
Capsule - initial treatment is 5 mg (placebo) - oral - once per day
Drug: ramipril
Capsule - initial treatment is 5 mg (active)- oral - once per day
Capsule - initial treatment is 5 mg (placebo) - oral - once per day
Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL
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
Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL
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
Percentage of Participants With U p/c <0.5 at 24 and 52 Weeks Following Conversion to Sirolimus
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
Percentage of Participants With Urinary Albumin to Creatinine Ratio (U Alb/c) <0.5 at 24 and 52 Weeks Following Conversion to SRL
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
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
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
U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
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
U Alb/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
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
Percentage of Participants Who Discontinued SRL Therapy at 24 and 52 Weeks Following Conversion to SRL
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
Abbreviated Modified Diet in Renal Disease (MDRD) Glomerular Filtration Rate (GFR) at Weeks 12, 24, and 52 Following Conversion to SRL
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
Fraction of Albumin (Milligrams Per Deciliter [mg/dL]) to Protein (mg/dL) in Urine at 24 and 52 Weeks After Conversion to SRL
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
Percentage of Participants With Potentially Clinically Important Blood Pressure (BP) Values by Diastolic and Systolic BP Category
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)
SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval
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
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)
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)
Change From Baseline in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) at 4, 12, 24, and 52 Weeks Following Conversion to SRL
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
Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event
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
Percentage of Participants With First BCAR at 24 and 52 Weeks Following Conversion to SRL
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
Number of Participants With BCAR by Severity of First BCAR
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
Percentage of Participants With Graft Loss at 24 and 52 Weeks Following Conversion to SRL
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
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)
Percentage of Participants With an Infection
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
Percentage of Participants With Angioedema
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
Percentage of Participants With Malignancy
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
Percentage of Participants With Hyperkalemia
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)
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.
| Milestone | Ramipril | Placebo |
|---|---|---|
| Started | 155 | 140 |
| Completed | 104 | 84 |
| Not completed | 51 | 56 |
| Withdrew: Lack of efficacy | 1 | 11 |
| Withdrew: Adverse event | 31 | 20 |
| Withdrew: Physician decision | 2 | 3 |
| Withdrew: Other - unspecified | 8 | 14 |
| Withdrew: Protocol violation | 3 | 1 |
| Withdrew: Withdrawal by subject | 6 | 7 |
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.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL | 6.2 (2.7 to 11.6) | 23.2 (15.7 to 31.4) |
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.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL | 14.4 (8.7 to 21.3) | 29.2 (21.2 to 37.6) |
Spot urine sample of protein and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Up to 24 weeks post-conversion | 92.0 | 77.8 |
| Up to 52 weeks post-conversion | 82.6 | 73.0 |
Spot urine sample of albumin and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Up to 24 weeks post-conversion | 95.7 | 89.7 |
| Up to 52 weeks post-conversion | 88.4 | 82.5 |
The U alb/c and U p/c must have been collected on the same day to be counted as the numerator.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Up to 24 weeks post-conversion | 91.3 | 77.0 |
| Up to 52 weeks post-conversion | 79.0 | 70.6 |
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.
| mg/mg | Ramipril | Placebo |
|---|---|---|
| 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 |
U alb/c was measured in mg/mg. Baseline U alb/c values were the last values of the pre-SRL conversion period.
| mg/mg | Ramipril | Placebo |
|---|---|---|
| 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 |
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).
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Up to 24 weeks post-conversion | 15.2 | 15.9 |
| Up to 52 weeks post-conversion | 19.6 | 28.6 |
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.
| mL/min/1.73 m^2 | Ramipril | Placebo |
|---|---|---|
| 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 |
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.
| (mg/dL)/(mg/dL) | Ramipril | Placebo |
|---|---|---|
| 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 |
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.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Baseline, Low DBP ≤50 mmHg (n=155,140) | 0.0 | 0.7 |
| Baseline, Low SBP: ≤90 mmHg (n=155,140) | 0.0 | 0.7 |
| Pre-SRL, Low DBP: ≤50 mmHg (n=152,135) | 0.0 | 0.7 |
| Pre-SRL, High DBP: ≥110 mmHg (n=152,135) | 0.0 | 1.5 |
| Pre-SRL, Low SBP: ≤90 mmHg (n=152,135) | 0.0 | 0.7 |
| Pre-SRL, High SBP: ≥180 mmHg (n=152,135) | 0.7 | 0.7 |
| On Therapy, Low DBP: ≤50 mmHg (n=138,126) | 3.6 | 2.4 |
| On Therapy, High DBP: ≥110 mmHg (n=138,126) | 0.0 | 1.6 |
| On Therapy, Low SBP: ≤90 mmHg (n=138,126) | 3.6 | 4.0 |
| On Therapy, High SBP: ≥180 mmHg (n=138,126) | 0.7 | 4.0 |
| Off Therapy, High DBP ≥110 mmHg (n=35,69) | 2.9 | 1.4 |
| Off Therapy, Low SBP: ≤90 mmHg (n=35,69) | 2.9 | 1.4 |
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.
| ng/mL | Ramipril |
|---|---|
| 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 |
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Baseline (n=155,140) | 1.3 | 1.4 |
| Pre-SRL (n=148,129) | 2.0 | 0.8 |
| On-Therapy (n=138,124) | 17.4 | 12.1 |
| Off-Therapy (n=33,34) | 9.1 | 2.9 |
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Baseline (n=155,140) | 5.8 | 1.4 |
| Pre-SRL (n=155,140) | 4.5 | 0.7 |
| On-Therapy (n=138,126) | 4.3 | 3.2 |
| Off-Therapy (n=136,122) | 1.5 | 4.1 |
Parameters assessed included (all fasting) total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-densitylipoprotein cholesterol (HDL-C).
| mmol/L | Ramipril | Placebo |
|---|---|---|
| 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 |
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.
| participants | Ramipril | Placebo |
|---|---|---|
| Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event | 13 | 5 |
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.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| 24 weeks post-conversion | 8.0 (4.2 to 13.3) | 0.8 (0.1 to 4.0) |
| 52 weeks post-conversion | 9.5 (5.3 to 15.1) | 3.2 (1.1 to 7.5) |
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.
| participants | Ramipril | Placebo |
|---|---|---|
| Post-SRL, AM BCAR, Grade I (mild) | 1 | 2 |
| Post-SRL, AM BCAR, Grade II (mod) | 0 | 1 |
| Post-SRL, AM BCAR, Grade III (severe) | 0 | 1 |
| Post-SRL, T-Cell BCAR, Grade I (mild) | 12 | 4 |
| Post-SRL (On-Therapy), AM BCAR, Grade I (mild) | 1 | 1 |
| Post-SRL (On-Therapy), AM BCAR, Grade II (mod) | 0 | 1 |
| Post-SRL (On-Therapy), T-Cell BCAR, Grade I (mild) | 10 | 3 |
Graft loss was defined as physical loss (nephrectomy orretransplantation), functional loss (requiring dialysis for ≥56days with no return of graft function), or death.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Week 24 | 0.0 | 0.0 |
| Week 52 | 0.0 | 0.8 |
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Baseline (n=155,140) | 45.8 | 36.4 |
| Pre-SRL (n=155,140) | 45.2 | 40.0 |
| On-Therapy (n=138,126) | 67.4 | 72.2 |
| Off-Therapy (n=136,122) | 62.5 | 68.9 |
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.)
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Percentage of Participants With an Infection | 54.2 | 56.4 |
Includes treatment-emergent adverse events based on categorization by the investigator as angioedema, regardless of the event preferred term in MedDRA.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Percentage of Participants With Angioedema | 1.3 | 1.4 |
Includes treatment-emergent adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferredterm in MedDRA.
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Percentage of Participants With Malignancy | 3.9 | 2.9 |
Hyperkalemia defined as serum potassium \>5.6 millimoles per liter (mmol/L)
| percentage of participants | Ramipril | Placebo |
|---|---|---|
| Baseline (n=155,140) | 0.0 | 1.4 |
| Pre-SRL (n=151,135) | 4.6 | 1.5 |
| On-Therapy (n=138,124) | 0.7 | 1.6 |
| Off-Therapy (n=34,36) | 2.9 | 0.0 |
Collected over Randomization through Week 52 following conversion to SRL. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ramipril | — | 50/155 (32.3%) | 134/155 (86.5%) |
| Placebo | — | 39/140 (27.9%) | 123/140 (87.9%) |
| Event | Ramipril | Placebo |
|---|---|---|
| Transplant rejectionImmune system disorders | 11/155 | 1/140 |
| DiarrhoeaGastrointestinal disorders | 4/155 | 2/140 |
| PyrexiaGeneral disorders | 4/155 | 0/140 |
| CellulitisInfections and infestations | 4/155 | 1/140 |
| Kidney transplant rejectionImmune system disorders | 3/155 | 3/140 |
| Basal cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 3/155 | 2/140 |
| Squamous cell carcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 3/155 | 1/140 |
| VomitingGastrointestinal disorders | 3/155 | 0/140 |
| Urinary tract infectionInfections and infestations | 3/155 | 1/140 |
| HeadacheNervous system disorders | 3/155 | 0/140 |
| Event | Ramipril | Placebo |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 40/155 | 37/140 |
| Oedema peripheralGeneral disorders | 27/155 | 30/140 |
| AcneSkin and subcutaneous tissue disorders | 18/155 | 25/140 |
| Upper respiratory tract infectionInfections and infestations | 27/155 | 16/140 |
| Blood creatinine increasedInvestigations | 24/155 | 11/140 |
| CoughRespiratory, thoracic and mediastinal disorders | 24/155 | 14/140 |
| DyslipidaemiaMetabolism and nutrition disorders | 14/155 | 19/140 |
| LeukopeniaBlood and lymphatic system disorders | 19/155 | 6/140 |
| HeadacheNervous system disorders | 19/155 | 16/140 |
| Mouth ulcerationGastrointestinal disorders | 12/155 | 17/140 |
| Age, Continuous(Years) | Ramipril | Placebo | Total |
|---|---|---|---|
| Mean | 46.8 ± 12.7 | 47.5 ± 12.9 | 47.1 ± 12.8 |
| Sex: Female, Male(Participants) | Ramipril | Placebo | Total |
|---|---|---|---|
| Female | 48 | 50 | 98 |
| Male | 107 | 90 | 197 |
This study is completed, as verified in Aug 2014. You cannot join it, but the record below documents what was studied.
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