Fibrosis in Renal Allografts
Recruitment status was: Recruiting
This prospective, randomized study, comparing sirolimus to cyclosporine in renal transplant recipients, has two major objectives:
-To determine the incidence and the degree of interstitialfibrosis and arteriosclerosis, as wel as the glomerular volume in protocol biopsies at 6 months in sirolimus-and in cyclosporine-treated renal allograft recipients, by means of quantitative computerized image analysis.
- To determine the prognostic implication of these morphologic changes.
- To study the expression of genes, involved in inflammation and fibrosis, in protocol biopsies at 6 months in sirolimus-and cyclosporine-treated renal allograft recipients.
Kidney Failure, Chronic
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Interstitial Fibrosis in Protocol Biopsies of Renal Allografts: A Prospective, Randomised Trial of Sirolimus Versus Cyclosporine.(Fibrasic)|
- The primary end-point of this study will be the cortical fractional interstitial fibrosis volume (V IntFib) in protocol biopsies at 6 months. The V IntFib will be determined on Sirius red stained slides by means of a computerized image analysis program,
- Secundary end-points:
- -Patient and graft-survival at one year.
- -The serum creatinine and the estimated creatinine
- clearance at 6 and 12 months.
- -The 24 hour proteinuria at 6 and 12 months.
- -The intimal area and arterial wall thickness in protocol
- biopsies at 6 months.
- -The glomerular volume in protocol biopsies at 6 months.
- -The incidence of acute rejection episodes during the
- first year.
- -The severity of acute rejection episodes according to
- the Banffâ 97 classification.
- -The incidence of infectious complications.
- -The incidence of hematological adverse effects.
- -The number of antihypertensive and lipid-lowering drugs
- at 6 and 12 months.
- -The incidence of treatment failure.
|Study Start Date:||May 2005|
|Estimated Study Completion Date:||July 2007|
Calcineurin inhibitors have significantly improved the one-year graft survival of renal allografts. However, chronic nephrotoxicity caused by calcineurin inhibitors contributes to the long-term decline in renal function in kidney transplant recipients. Approximately ninety percent of the protocol biopsies of renal allografts, performed at 18 months post transplantation, show histological lesions of chronic calcineurin nephrotoxicity . In recent years, two new non-nephrotoxic immunosuppressive drugs, i.e. mycophenolate mofetil and sirolimus, have become available for the prophylaxis of graft rejection in renal transplantation.
Three randomized clinical trials, comparing cyclosporine with sirolimus in combination with mycophenolate mofetil, reported a superior graft function at one year in sirolimus treated renal allograft recipients. However, data on long-term graft survival and histological lesions of protocol biopsies in sirolimus-treated renal transplant recipients, are currently lacking.
In analogy with previous observations in native kidney disease, Grimm et al. recently reported that interstitial fibrosis in protocol biopsies of renal allografts, at 6 months post transplantation, significantly inversely correlates with the subsequent graft survival One hundred recipients of a first renal allograft will be randomized to an immunosuppressive protocol based on cyclosporine (50 patients) or sirolimus (50 patients). Concommittant immunosuppression will be similar in both groups, and consists of Daclizumab as induction treatment (five iv gifts every two weeks), and mycophenolate mophetil and steroids as maintenance immunosuppression.
Randomization will be performed by centre to avoid centre-related bias. All patients will complete a follow-up of 12 months. Two core biopsies of the graft will be obtained in each recipient, at implantation and at 6 months. Serum creatinine and the estimated creatinine clearance (by the Nankivell and the Jellife method) will be monthly recorded.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00493194
|University Hospital Antwerp|
|Edegem, Antwerp, Belgium, 9260|
|University Hospital Brussels|
|Brussels (Jette), Brabant, Belgium, 1090|
|University Hospital Gent|
|Gent, Oost-Vlaanderen, Belgium, 9000|
|Principal Investigator:||Jean-Louis Bosmans, M.D. Ph.D.||University Hospital, Antwerp|