Clinical trial NCT00502242: Study Evaluating The Effect Of Ramipril On Urinary Protein Excretion In Renal Transplant Patients Converted To Sirolimus
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplant
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2007-07-17
Enrollment: 229
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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 \< 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.

Primary outcomes:
measure: Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL
timeFrame: From Day 1 of SRL conversion to 52 weeks after conversion
Secondary outcomes:
measure: Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL
timeFrame: From Day 1 of SRL conversion to 52 weeks after conversion
measure: Percentage of Participants With U p/c <0.5 at 24 and 52 Weeks Following Conversion to Sirolimus
timeFrame: 24 weeks and 52 weeks after conversion
measure: Percentage of Participants With Urinary Albumin to Creatinine Ratio (U Alb/c) <0.5 at 24 and 52 Weeks Following Conversion to SRL
timeFrame: 24 weeks and 52 weeks after conversion
measure: 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
timeFrame: 24 weeks and 52 weeks after conversion
measure: U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
timeFrame: Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion
measure: U Alb/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL
timeFrame: Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion
measure: Percentage of Participants Who Discontinued SRL Therapy at 24 and 52 Weeks Following Conversion to SRL
timeFrame: 24 weeks and 52 weeks after conversion
measure: Abbreviated Modified Diet in Renal Disease (MDRD) Glomerular Filtration Rate (GFR) at Weeks 12, 24, and 52 Following Conversion to SRL
timeFrame: 12, 24, and 52 weeks following conversion
measure: Fraction of Albumin (Milligrams Per Deciliter [mg/dL]) to Protein (mg/dL) in Urine at 24 and 52 Weeks After Conversion to SRL
timeFrame: 24 weeks and 52 weeks after conversion
measure: Percentage of Participants With Potentially Clinically Important Blood Pressure (BP) Values by Diastolic and Systolic BP Category
timeFrame: 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)
measure: SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval
timeFrame: From Day 1 of SRL conversion to 52 weeks after conversion
measure: Percentage of Participants With Hemoglobin Levels ≤100 Grams Per Liter (g/L)
timeFrame: 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)
measure: Percentage of Participants Using Red Blood Cell Production Stimulants (Erythropoiesis Stimulating Agents [ESAs])
timeFrame: 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)
measure: Change From Baseline in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) at 4, 12, 24, and 52 Weeks Following Conversion to SRL
timeFrame: 4, 12, 24, and 52 weeks after conversion
measure: Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event
timeFrame: From Day 1 of SRL conversion to 52 weeks after conversion
measure: Percentage of Participants With First BCAR at 24 and 52 Weeks Following Conversion to SRL
timeFrame: 24 weeks and 52 weeks after conversion
measure: Number of Participants With BCAR by Severity of First BCAR
timeFrame: From Day 1 of SRL conversion to 52 weeks after conversion
measure: Percentage of Participants With Graft Loss at 24 and 52 Weeks Following Conversion to SRL
timeFrame: 24 weeks and 52 weeks after conversion
measure: Percentage of Participants Using Statins
timeFrame: 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)
measure: Percentage of Participants With an Infection
timeFrame: From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
measure: Percentage of Participants With Angioedema
timeFrame: From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
measure: Percentage of Participants With Malignancy
timeFrame: From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion
measure: Percentage of Participants With Hyperkalemia
timeFrame: 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)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: Los Angeles
country: United States
facility: Pfizer Investigational Site
state: California
city: San Francisco
country: United States
facility: Pfizer Investigational Site
state: California
city: Aurora
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Denver
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Gainesville
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Chicago
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: Iowa City
country: United States
facility: Pfizer Investigational Site
state: Iowa
city: Lexington
country: United States
facility: Pfizer Investigational Site
state: Kentucky
city: Portland
country: United States
facility: Pfizer Investigational Site
state: Maine
city: Boston
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Springfield
country: United States
facility: Pfizer Investigational Site
state: Massachusetts
city: Gosse Pointe
country: United States
facility: Pfizer Investigational Site
state: Michigan
city: Buffalo
country: United States
facility: Pfizer Investigational Site
state: New York
city: Valhalla
country: United States
facility: Pfizer Investigational Site
state: New York
city: Cleveland
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Pfizer Investigational Site
state: Ohio
city: Harrisburg
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Providence
country: United States
facility: Pfizer Investigational Site
state: Rhode Island
city: Charleston
country: United States
facility: Pfizer Investigational Site
state: South Carolina
city: Capital Federal
country: Argentina
facility: Pfizer Investigational Site
state: Buenos Aires
city: San Martin
country: Argentina
facility: Pfizer Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Pfizer Investigational Site
city: Cordoba
country: Argentina
facility: Pfizer Investigational Site
city: Córdoba
country: Argentina
facility: Pfizer Investigational Site
city: Brisbane
country: Australia
facility: Pfizer Investigational Site
state: Queensland
city: North Terrace
country: Australia
facility: Pfizer Investigational Site
city: Woodville South
country: Australia
facility: Pfizer Investigational Site
city: Linz
country: Austria
facility: Pfizer Investigational Site
city: Rio de Janeiro
country: Brazil
facility: Pfizer Investigational Site
state: RJ
city: Porto Alegre
country: Brazil
facility: Pfizer Investigational Site
state: RS
city: Porto Alegre
country: Brazil
facility: Pfizer Investigational Site
state: RS
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Sao Paulo
country: Brazil
facility: Pfizer Investigational Site
state: SP
city: Montreal
country: Canada
facility: Pfizer Investigational Site
state: Quebec
city: Erlangen
country: Germany
facility: Pfizer Investigational Site
city: Szeged
country: Hungary
facility: Pfizer Investigational Site
city: Petach Tikva
country: Israel
facility: Pfizer Investigational Site
city: Mexico City
country: Mexico
facility: Pfizer Investigational Site
city: Veracruz
country: Mexico
facility: Pfizer Investigational Site
city: Szczecin
country: Poland
facility: Pfizer Investigational Site
city: Johannesburg
country: South Africa
facility: Pfizer Investigational Site
state: Gauteng
city: Cape Town
country: South Africa
facility: Pfizer Investigational Site
state: Western Cape
city: Cape Town
country: South Africa
facility: Pfizer Investigational Site
state: Western Cape
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.