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Fibrosis in Renal Allografts

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: NCT00493194
Recruitment Status : Unknown
Verified October 2005 by University Hospital, Antwerp.
Recruitment status was:  Recruiting
First Posted : June 28, 2007
Last Update Posted : November 26, 2008
Wyeth is now a wholly owned subsidiary of Pfizer
Hoffmann-La Roche
Information provided by:
University Hospital, Antwerp

Brief Summary:

This prospective, randomized study, comparing sirolimus to cyclosporine in renal transplant recipients, has two major objectives:

  1. -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.
  2. 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.

Condition or disease Intervention/treatment Phase
Kidney Failure, Chronic Transplantation Immunosuppression Interstitial Fibrosis Drug: sirolimus Drug: cyclosporine Drug: daclizumab Phase 4

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Interstitial Fibrosis in Protocol Biopsies of Renal Allografts: A Prospective, Randomised Trial of Sirolimus Versus Cyclosporine.(Fibrasic)
Study Start Date : May 2005
Estimated Study Completion Date : July 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Biopsy

Primary Outcome Measures :
  1. 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,

Secondary Outcome Measures :
  1. Secundary end-points:
  2. -Patient and graft-survival at one year.
  3. -The serum creatinine and the estimated creatinine
  4. clearance at 6 and 12 months.
  5. -The 24 hour proteinuria at 6 and 12 months.
  6. -The intimal area and arterial wall thickness in protocol
  7. biopsies at 6 months.
  8. -The glomerular volume in protocol biopsies at 6 months.
  9. -The incidence of acute rejection episodes during the
  10. first year.
  11. -The severity of acute rejection episodes according to
  12. the Banffâ 97 classification.
  13. -The incidence of infectious complications.
  14. -The incidence of hematological adverse effects.
  15. -The number of antihypertensive and lipid-lowering drugs
  16. at 6 and 12 months.
  17. -The incidence of treatment failure.

Information from the National Library of Medicine

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

Inclusion Criteria:

  1. Recipients of a renal allograft, with a minimum age of 18 years.
  2. Male or female recipients. Women of child-bearing age must practice adequate contraception
  3. For renal allografts from living donors, at least one HLA-mismatch is required.
  4. Written informed consent, compliant with local regulations.

Exclusion Criteria:

  1. Recipients of a second or third renal allograft, with a past history of graft failure due to rejection.
  2. Recipients of a renal allograft from a haplotype-identical living donor or a non-heart beating donor.
  3. Cold ischemia time > 24 hours
  4. Recipients of a kidney from donors ≥ 65 years of age
  5. Recipients of multiple organs.
  6. Pregnant women.
  7. Immunological high-risk recipients, defined as current or historical PRA > 50 %
  8. Recipients with focal segmental sclerosis as primary renal disease.
  9. Recipients with leucopenia (WBC < 3000/mm³), thrombocytopenia (Thr < 100.000/mm³),or hyperlipidemia (Tot Chol > 300 mg/dl or Triglycerides > 300 mg/dl)
  10. Previous history of malignancy, except completely excised basocellular skin tumor
  11. Chronic active infection.
  12. Inadequate compliance to treatment.
  13. Use of specific drugs: Terfenadine, pimozide, astemizole, fluconazole, ketoconazole and cimetidine.

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): NCT00493194

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Contact: Jean-Louis Bosmans, MD Ph.D ..32/3/821 37 92
Contact: Angelika Jurgens, Coordinator ..32/3/821.34.68

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University Hospital Antwerp Recruiting
Edegem, Antwerp, Belgium, 9260
Contact: Jean-Louis Bosmans, M.D. Ph.D.    ..32/3/821 37 92   
Contact: Angelika Jurgens, Coordinator    ..32/3/821.34.68   
Principal Investigator: Jean-Louis Bosmans, MD. Ph.D.         
University Hospital Brussels Recruiting
Brussels (Jette), Brabant, Belgium, 1090
Contact: Jacques Sennesael, M.D.    ..32/2/477.60.55   
Contact: Katrien Van Bever, Study-nurse    ..32/2/477.60.55   
Principal Investigator: Jacques Sennesael, M.D.         
University Hospital Gent Recruiting
Gent, Oost-Vlaanderen, Belgium, 9000
Contact: Patrick Peeters, M.D.    ..32/9/240.45.13   
Contact: Cathy Vandermeulen, Study-Nurse    ..32/9/240.61.68   
Principal Investigator: Patrick Peeters, M.D.         
Sponsors and Collaborators
University Hospital, Antwerp
Wyeth is now a wholly owned subsidiary of Pfizer
Hoffmann-La Roche
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Principal Investigator: Jean-Louis Bosmans, M.D. Ph.D. University Hospital, Antwerp

Publications of Results:
Layout table for additonal information Identifier: NCT00493194    
Other Study ID Numbers: 2004-004115-38
First Posted: June 28, 2007    Key Record Dates
Last Update Posted: November 26, 2008
Last Verified: October 2005
Keywords provided by University Hospital, Antwerp:
Cyclosporine toxicity
Interstitial Fibrosis
Chronic allograft nephropathy
Additional relevant MeSH terms:
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Lung Diseases, Interstitial
Renal Insufficiency
Kidney Failure, Chronic
Pathologic Processes
Kidney Diseases
Urologic Diseases
Renal Insufficiency, Chronic
Lung Diseases
Respiratory Tract Diseases
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Anti-Bacterial Agents
Antibiotics, Antineoplastic
Antineoplastic Agents