Ignite Creation Date:
2024-05-05 @ 11:19 AM
Last Modification Date:
2024-10-26 @ 9:04 AM
Study NCT ID:
NCT00005010
Status:
COMPLETED
Last Update Posted:
2013-01-25
First Post:
2000-03-28
Brief Title:
Prevention of Kidney Transplant Rejection
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institute of Allergy and Infectious Diseases NIAID
Study Overview
Official Title:
An Interventional Trial in Established Chronic Renal Allograft Rejection
Status:
COMPLETED
Status Verified Date:
2013-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
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 mgday Irbesartan is initiated at 150 mgday and is titred to 300 mgday 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 50 mgdl 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
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 mgday Irbesartan is initiated at 150 mgday and is titred to 300 mgday 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 50 mgdl 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None