Prevention of Kidney Transplant Rejection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005010
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : January 25, 2013
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:

The purpose of this study is to see how effective 2 drugs, irbesartan and pravastatin, are at slowing kidney transplant failure.

Many kidney transplant patients have some type of chronic rejection. Chronic rejection is a disease that causes scarring and damage to the kidney. Over time, chronic rejection can lead to kidney failure, making it necessary for patients to start dialysis and possibly receive another kidney transplant. Doctors would like to see whether irbesartan and pravastatin can slow this damage and prevent kidney failure in patients with signs of chronic rejection.

Condition or disease Intervention/treatment Phase
End-Stage Renal Disease Chronic Allograft Nephropathy Drug: Irbesartan Drug: Pravastatin Phase 3

Detailed Description:

Renal graft failure due to chronic rejection, also known as chronic allograft nephropathy, is one of the leading causes for repeat renal transplantation. Chronic rejection is characterized by progressive fibrosis and scarring. Renal biopsies of patients undergoing chronic rejection show greater expression of profibrotic cytokines, including TGF-beta and PDGF, than normal kidney tissue. Moreover, the cytokine activity of chronic rejection resembles that of other fibrosing renal diseases. Angiotensin converting enzyme inhibitors (ACEinh) and HMG-CoA reductase inhibitors have been shown to protect effectively against other types of fibrotic disease. These drugs may protect against fibrosis and preserve renal function in renal transplant patients with chronic rejection, in part by blocking activation of TGF-beta and PDGF. This study evaluates the impact of irbesartan (an AII-RB which acts similar to an ACEinh) and pravastatin on the clinical progression of chronic rejection and on the expression of TGF-beta, PDGF, and connective tissue genes in the chronically rejecting kidney.

Prior to intervention, patients undergo a transplant renal biopsy to: 1) confirm the presence of chronic renal allograft nephropathy and 2) quantify baseline mRNA levels for TGF-beta, PDGF, and selected cytokines and connective tissue components. Patients are randomized to 4 arms: Group 1 receives pravastatin placebo plus irbesartan placebo; Group 2 receives pravastatin plus irbesartan placebo; Group 3 receives pravastatin placebo plus irbesartan; and Group 4 receives pravastatin plus irbesartan. Pravastatin is administered at a dose of 20 mg/day. Irbesartan is initiated at 150 mg/day and is titred to 300 mg/day after 2 weeks. Patients are evaluated routinely for serum creatinine and potassium levels, blood pressure, and other markers of kidney function. In addition, they are monitored for toxicities and adverse events, particularly an early rise in serum creatinine or muscle enzyme changes. At Month 6, or when serum creatinine has risen above 5.0 mg/dl if that is earlier, a repeat transplant kidney biopsy is obtained to compare to baseline. Changes in chronic allograft nephropathy and cytokine mRNA levels are evaluated to determine any correlation between clinical effect and changes in activity of profibrotic pathways. Study endpoints are death or renal failure manifested by initiation of dialysis or retransplantation.

Study Type : Interventional  (Clinical Trial)
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: An Interventional Trial in Established Chronic Renal Allograft Rejection
Actual Study Completion Date : March 2004

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Primary Outcome Measures :
  1. death, or renal failure manifested by initiation of dialysis or retransplantation. [ Time Frame: Randomization to End of Study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

You may be eligible for this study if you:

  • Are at least 18 years old.
  • Received a kidney transplant at least 1 year prior to study entry.
  • Have been diagnosed with chronic rejection following kidney transplant and within 6 months prior to study entry.
  • Have been receiving a stable immunosuppressive medication regimen for 1 month prior to study entry that includes at least cyclosporine or tacrolimus and prednisone.
  • Have high blood pressure.
  • Agree to use an effective method of birth control during the study.

Exclusion Criteria

You will not be eligible for this study if you:

  • Are participating in another study with required tests or treatments.
  • Cannot take ACE inhibitors or HMG-CoA reductase inhibitors.
  • Absolutely must take ACE inhibitors or HMG-CoA reductase inhibitors.
  • Have a serious disease or medical condition.
  • Are pregnant.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005010

United States, Maryland
Ilene Blechman-Krom
Rockville, Maryland, United States, 20850
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00005010     History of Changes
Other Study ID Numbers: DAIT CR01
First Posted: August 31, 2001    Key Record Dates
Last Update Posted: January 25, 2013
Last Verified: January 2013

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency, Chronic
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antihypertensive Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists