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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
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
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
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
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
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
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
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
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
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
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
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
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)
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])
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
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
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
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
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
Timepoint [18] 0 0
24 weeks and 52 weeks after conversion
Secondary outcome [19] 0 0
Percentage of Participants Using Statins
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
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
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
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
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
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00502242
Trial related presentations / publications
Mandelbrot DA, Alberu J, Barama A, Marder BA, Silva HT Jr, Flechner SM, Flynn A, Healy C, Li H, Tortorici MA, Schulman SL. Effect of Ramipril on Urinary Protein Excretion in Maintenance Renal Transplant Patients Converted to Sirolimus. Am J Transplant. 2015 Dec;15(12):3174-84. doi: 10.1111/ajt.13384. Epub 2015 Jul 14.
Public notes

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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00502242