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Study Evaluating The Effect Of Ramipril On Urinary Protein Excretion In Renal Transplant Patients Converted To Sirolimus

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ClinicalTrials.gov Identifier: NCT00502242
Recruitment Status : Completed
First Posted : July 17, 2007
Results First Posted : August 27, 2014
Last Update Posted : August 27, 2014
Sponsor:
Information provided by (Responsible Party):
Pfizer

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Kidney Transplant
Intervention: Drug: ramipril

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Eligible participants were randomly assigned in a Double-Blind fashion to the Ramipril treatment group or the Placebo control group.

Reporting Groups
  Description
Ramipril Participants were receiving cyclosporine (CsA) or tacrolimus (TAC) and either mycophenolate mofetil (MMF), mycophenolate sodium (MPS), or azathioprine (AZA) or steroids dosed per center’s standard of care. Participants received ramipril, 5 or 10 milligrams per day (mg/d) orally (PO). 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of sirolimus [SRL] initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 nanograms per milliliter [ng/mL] less than [<]1 year post-transplant [PT], 5-15 ng/mL greater than or equal to [≥]1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if urinary protein to creatinine ratio (U p/c) was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Placebo Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.

Participant Flow:   Overall Study
    Ramipril   Placebo
STARTED   155   140 
COMPLETED   104   84 
NOT COMPLETED   51   56 
Lack of Efficacy                1                11 
Adverse Event                31                20 
Physician Decision                2                3 
Other - Unspecified                8                14 
Protocol Violation                3                1 
Withdrawal by Subject                6                7 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ramipril Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received ramipril 5 or 10 mg/d PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Ramipril was increased to 10-20 mg if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Placebo Participants were receiving CsA or TAC and either MMF, MPS, or AZA or steroids dosed per center’s standard of care. Participants received double-blinded placebo, 1 capsule (5 or 10 mg/day), PO. 2-6 weeks after randomization, participants stopped TAC or CsA (within 21 days of SRL initiation) and received SRL, PO, 2-4 mg/d (6-12 mg on Day 1 if TAC or CsA withdrawn abruptly) to achieve target trough levels (7-15 ng/mL <1 year PT, 5-15 ng/mL ≥1 year PT) for up to 52 weeks. Placebo dose was doubled if U p/c was ≥0.5. If U p/c ≥0.5 persisted, losartan 50 mg/d was added; if U p/c ≥0.5 still persisted, losartan was increased to 100 mg/d. If then U p/c <0.5 was not maintained, study medication was discontinued and participant entered off-therapy phase of study.
Total Total of all reporting groups

Baseline Measures
   Ramipril   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 155   140   295 
Age 
[Units: Years]
Mean (Standard Deviation)
 46.8  (12.7)   47.5  (12.9)   47.1  (12.8) 
Gender 
[Units: Participants]
     
Female   48   50   98 
Male   107   90   197 


  Outcome Measures

1.  Primary:   Percentage of Participants Who Had Initiated Losartan Therapy at 52 Weeks Following Conversion to SRL   [ Time Frame: From Day 1 of SRL conversion to 52 weeks after conversion ]

2.  Secondary:   Percentage of Participants Who Had a Dose Escalation in Randomized Test Article (Ramipril or Placebo) by 52 Weeks Following Conversion to SRL   [ Time Frame: From Day 1 of SRL conversion to 52 weeks after conversion ]

3.  Secondary:   Percentage of Participants With U p/c <0.5 at 24 and 52 Weeks Following Conversion to Sirolimus   [ Time Frame: 24 weeks and 52 weeks after conversion ]

4.  Secondary:   Percentage of Participants With Urinary Albumin to Creatinine Ratio (U Alb/c) <0.5 at 24 and 52 Weeks Following Conversion to SRL   [ Time Frame: 24 weeks and 52 weeks after conversion ]

5.  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   [ Time Frame: 24 weeks and 52 weeks after conversion ]

6.  Secondary:   U p/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL   [ Time Frame: Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion ]

7.  Secondary:   U Alb/c at Baseline and Weeks 3, 4, 8, 12, 24, 30, 36, and 52 Following Conversion to SRL   [ Time Frame: Baseline and 3, 4, 8, 12, 24, 30, 36, and 52 weeks after conversion ]

8.  Secondary:   Percentage of Participants Who Discontinued SRL Therapy at 24 and 52 Weeks Following Conversion to SRL   [ Time Frame: 24 weeks and 52 weeks after conversion ]

9.  Secondary:   Abbreviated Modified Diet in Renal Disease (MDRD) Glomerular Filtration Rate (GFR) at Weeks 12, 24, and 52 Following Conversion to SRL   [ Time Frame: 12, 24, and 52 weeks following conversion ]

10.  Secondary:   Fraction of Albumin (Milligrams Per Deciliter [mg/dL]) to Protein (mg/dL) in Urine at 24 and 52 Weeks After Conversion to SRL   [ Time Frame: 24 weeks and 52 weeks after conversion ]

11.  Secondary:   Percentage of Participants With Potentially Clinically Important Blood Pressure (BP) Values by Diastolic and Systolic BP Category   [ 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) ]

12.  Secondary:   SRL Time-Normalized Trough Concentration (Cmin,TN) by Time Interval   [ Time Frame: From Day 1 of SRL conversion to 52 weeks after conversion ]

13.  Secondary:   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) ]

14.  Secondary:   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) ]

15.  Secondary:   Change From Baseline in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) at 4, 12, 24, and 52 Weeks Following Conversion to SRL   [ Time Frame: 4, 12, 24, and 52 weeks after conversion ]

16.  Secondary:   Biopsy-Confirmed Acute Rejection (BCAR) - Number of Participants With an Event   [ Time Frame: From Day 1 of SRL conversion to 52 weeks after conversion ]

17.  Secondary:   Percentage of Participants With First BCAR at 24 and 52 Weeks Following Conversion to SRL   [ Time Frame: 24 weeks and 52 weeks after conversion ]

18.  Secondary:   Number of Participants With BCAR by Severity of First BCAR   [ Time Frame: From Day 1 of SRL conversion to 52 weeks after conversion ]

19.  Secondary:   Percentage of Participants With Graft Loss at 24 and 52 Weeks Following Conversion to SRL   [ Time Frame: 24 weeks and 52 weeks after conversion ]

20.  Secondary:   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) ]

21.  Secondary:   Percentage of Participants With an Infection   [ Time Frame: From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion ]

22.  Secondary:   Percentage of Participants With Angioedema   [ Time Frame: From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion ]

23.  Secondary:   Percentage of Participants With Malignancy   [ Time Frame: From Day 1 of Ramipril/Placebo to 52 weeks after SRL conversion ]

24.  Secondary:   Percentage of Participants With Hyperkalemia   [ 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) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00502242     History of Changes
Other Study ID Numbers: 0468E5-4439
B1741001
First Submitted: July 16, 2007
First Posted: July 17, 2007
Results First Submitted: August 13, 2014
Results First Posted: August 27, 2014
Last Update Posted: August 27, 2014