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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00502242




Registration number
NCT00502242
Ethics application status
Date submitted
16/07/2007
Date registered
17/07/2007
Date last updated
27/08/2014

Titles & IDs
Public title
Study Evaluating The Effect Of Ramipril On Urinary Protein Excretion In Renal Transplant Patients Converted To Sirolimus
Scientific 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
Secondary ID [1] 0 0
B1741001
Secondary ID [2] 0 0
0468E5-4439
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Kidney Transplant 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ramipril
Treatment: Drugs - ramipril

Active comparator: A - 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


Treatment: Drugs: ramipril
Capsule - initial treatment is 5 mg (active)- oral - once per day

Treatment: Drugs: ramipril
Capsule - initial treatment is 5 mg (placebo) - oral - once per day
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
From Day 1 of SRL conversion to 52 weeks after conversion
Secondary outcome [1] 0 0
Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
From Day 1 of SRL conversion to 52 weeks after conversion
Secondary outcome [2] 0 0
Percentage of Participants With U p/c <0.5 at 24 and 52 Weeks Following Conversion to Sirolimus
Assessment method [2] 0 0
Spot urine sample of protein and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.
Timepoint [2] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [3] 0 0
Percentage of Participants With Urinary Albumin to Creatinine Ratio (U Alb/c) <0.5 at 24 and 52 Weeks Following Conversion to SRL
Assessment method [3] 0 0
Spot urine sample of albumin and creatinine concentrations were obtained during the pre-SRL conversion period and after conversion.
Timepoint [3] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [4] 0 0
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
Assessment method [4] 0 0
The U alb/c and U p/c must have been collected on the same day to be counted as the numerator.
Timepoint [4] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [5] 0 0
U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion
Secondary outcome [6] 0 0
U Alb/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
Assessment method [6] 0 0
U alb/c was measured in mg/mg. Baseline U alb/c values were the last values of the pre-SRL conversion period.
Timepoint [6] 0 0
Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion
Secondary outcome [7] 0 0
Percentage of Participants Who Discontinued SRL Therapy at 24 and 52 Weeks Following Conversion to SRL
Assessment method [7] 0 0
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).
Timepoint [7] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [8] 0 0
Abbreviated Modified Diet in Renal Disease (MDRD) Glomerular Filtration Rate (GFR) at Weeks 12, 24, and 52 Following Conversion to SRL
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
12, 24, and 52 weeks following conversion
Secondary outcome [9] 0 0
Fraction of Albumin (Milligrams Per Deciliter [mg/dL]) to Protein (mg/dL) in Urine at 24 and 52 Weeks After Conversion to SRL
Assessment method [9] 0 0
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 '\
Timepoint [9] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [10] 0 0
Percentage of Participants With Potentially Clinically Important Blood Pressure (BP) Values by Diastolic and Systolic BP Category
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
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)
Secondary outcome [11] 0 0
SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
From Day 1 of SRL conversion to 52 weeks after conversion
Secondary outcome [12] 0 0
Percentage of Participants With Hemoglobin Levels =100 Grams Per Liter (g/L)
Assessment method [12] 0 0
Timepoint [12] 0 0
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)
Secondary outcome [13] 0 0
Percentage of Participants Using Red Blood Cell Production Stimulants (Erythropoiesis Stimulating Agents [ESAs])
Assessment method [13] 0 0
Timepoint [13] 0 0
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)
Secondary outcome [14] 0 0
Change From Baseline in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) at 4, 12, 24, and 52 Weeks Following Conversion to SRL
Assessment method [14] 0 0
Parameters assessed included (all fasting) total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-densitylipoprotein cholesterol (HDL-C).
Timepoint [14] 0 0
4, 12, 24, and 52 weeks after conversion
Secondary outcome [15] 0 0
Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event
Assessment method [15] 0 0
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.
Timepoint [15] 0 0
From Day 1 of SRL conversion to 52 weeks after conversion
Secondary outcome [16] 0 0
Percentage of Participants With First BCAR at 24 and 52 Weeks Following Conversion to SRL
Assessment method [16] 0 0
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.
Timepoint [16] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [17] 0 0
Number of Participants With BCAR by Severity of First BCAR
Assessment method [17] 0 0
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.
Timepoint [17] 0 0
From Day 1 of SRL conversion to 52 weeks after conversion
Secondary outcome [18] 0 0
Percentage of Participants With Graft Loss at 24 and 52 Weeks Following Conversion to SRL
Assessment method [18] 0 0
Graft loss was defined as physical loss (nephrectomy orretransplantation), functional loss (requiring dialysis for =56days with no return of graft function), or death.
Timepoint [18] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [19] 0 0
Percentage of Participants Using Statins
Assessment method [19] 0 0
Timepoint [19] 0 0
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)
Secondary outcome [20] 0 0
Percentage of Participants With an Infection
Assessment method [20] 0 0
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.)
Timepoint [20] 0 0
From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
Secondary outcome [21] 0 0
Percentage of Participants With Angioedema
Assessment method [21] 0 0
Includes treatment-emergent adverse events based on categorization by the investigator as angioedema, regardless of the event preferred term in MedDRA.
Timepoint [21] 0 0
From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
Secondary outcome [22] 0 0
Percentage of Participants With Malignancy
Assessment method [22] 0 0
Includes treatment-emergent adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferredterm in MedDRA.
Timepoint [22] 0 0
From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
Secondary outcome [23] 0 0
Percentage of Participants With Hyperkalemia
Assessment method [23] 0 0
Hyperkalemia defined as serum potassium \>5.6 millimoles per liter (mmol/L)
Timepoint [23] 0 0
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)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2013
Sample size
Target
Accrual to date
Final
229
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Brisbane
Recruitment hospital [2] 0 0
Pfizer Investigational Site - North Terrace
Recruitment hospital [3] 0 0
Pfizer Investigational Site - Woodville South
Recruitment postcode(s) [1] 0 0
4029 - Brisbane
Recruitment postcode(s) [2] 0 0
5000 - North Terrace
Recruitment postcode(s) [3] 0 0
SA 5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Iowa
Country [6] 0 0
United States of America
State/province [6] 0 0
Kentucky
Country [7] 0 0
United States of America
State/province [7] 0 0
Maine
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
New York
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Rhode Island
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
Argentina
State/province [15] 0 0
Buenos Aires
Country [16] 0 0
Argentina
State/province [16] 0 0
Cordoba
Country [17] 0 0
Argentina
State/province [17] 0 0
Córdoba
Country [18] 0 0
Austria
State/province [18] 0 0
Linz
Country [19] 0 0
Brazil
State/province [19] 0 0
RJ
Country [20] 0 0
Brazil
State/province [20] 0 0
RS
Country [21] 0 0
Brazil
State/province [21] 0 0
SP
Country [22] 0 0
Canada
State/province [22] 0 0
Quebec
Country [23] 0 0
Germany
State/province [23] 0 0
Erlangen
Country [24] 0 0
Hungary
State/province [24] 0 0
Szeged
Country [25] 0 0
Israel
State/province [25] 0 0
Petach Tikva
Country [26] 0 0
Mexico
State/province [26] 0 0
Mexico City
Country [27] 0 0
Mexico
State/province [27] 0 0
Veracruz
Country [28] 0 0
Poland
State/province [28] 0 0
Szczecin
Country [29] 0 0
South Africa
State/province [29] 0 0
Gauteng
Country [30] 0 0
South Africa
State/province [30] 0 0
Western Cape

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT00502242