Kidney Failure, ChronicPhase 4NCT00493194
Fibrosis in Renal Allografts
A Phase 4 study testing sirolimus, cyclosporine and daclizumab in people with Kidney Failure, Chronic and Transplantation, run by University Hospital, Antwerp at 3 sites in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Kidney Failure, Chronic, Transplantation, Immunosuppression
- What is being tested?
- sirolimus, cyclosporine and daclizumab
- How many people
- 100 participants
- Where
- 3 sitesBelgium
- Study dates
- May 2005to Jul 2007
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Recipients of a renal allograft, with a minimum age of 18 years.
- Male or female recipients. Women of child-bearing age must practice adequate contraception
- For renal allografts from living donors, at least one HLA-mismatch is required.
- Written informed consent, compliant with local regulations.
Who cannot join
- Recipients of a second or third renal allograft, with a past history of graft failure due to rejection.
- Recipients of a renal allograft from a haplotype-identical living donor or a non-heart beating donor.
- Cold ischemia time > 24 hours
- Recipients of a kidney from donors ≥ 65 years of age
- Recipients of multiple organs.
- Pregnant women.
Show all 13Show fewer
- Immunological high-risk recipients, defined as current or historical PRA > 50 %
- Recipients with focal segmental sclerosis as primary renal disease.
- Recipients with leucopenia (WBC < 3000/mm³), thrombocytopenia (Thr < 100.000/mm³),or hyperlipidemia (Tot Chol > 300 mg/dl or Triglycerides > 300 mg/dl)
- Previous history of malignancy, except completely excised basocellular skin tumor
- Chronic active infection.
- Inadequate compliance to treatment.
- Use of specific drugs: Terfenadine, pimozide, astemizole, fluconazole, ketoconazole and cimetidine.
Trial locations and contacts
3 sites in 1 country.
Belgium3 sites, 3 recruiting
- Recruiting
University Hospital Brussels
Brussels (Jette), Brabant, 1090
Jacques Sennesael, M.D., ..32/2/477.60.55, hemofsn@az.vub.ac.be
Katrien Van Bever, Study-nurse, ..32/2/477.60.55, Katrien.VanBever@az.vub.ac.be
- Recruiting
University Hospital Antwerp
Edegem, Antwerp, 9260
Jean-Louis Bosmans, M.D. Ph.D., ..32/3/821 37 92, JeanLouis.Bosmans@ua.ac.be
Angelika Jurgens, Coordinator, ..32/3/821.34.68, Angelika.Jurgens@uza.be
- Recruiting
University Hospital Gent
Ghent, Oost-Vlaanderen, 9000
Patrick Peeters, M.D., ..32/9/240.45.13, p.peeters@ugent.be
Cathy Vandermeulen, Study-Nurse, ..32/9/240.61.68, Cathy.Vandermeulen@uzgent.be
About this study
Official title: Interstitial Fibrosis in Protocol Biopsies of Renal Allografts: A Prospective, Randomised Trial of Sirolimus Versus Cyclosporine.(Fibrasic)
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.
Read the 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.
- Being tested
- sirolimus, cyclosporine, daclizumab
- Keywords
- Cyclosporine toxicity, Interstitial Fibrosis, Chronic allograft nephropathy, Sirolimus
- Medical subject headings
- Kidney Failure, Chronic, Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sirolimusDrug
cyclosporineDrug
daclizumabDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
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 outcomes (17)
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2007 (estimated)
- Study startMay 2005
- Study completionJul 2007 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- More trials run by University Hospital, AntwerpThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Antwerp
- Sponsor type
- University, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer, Hoffmann-La Roche
- Investigators
- Jean-Louis Bosmans, M.D. Ph.D., Principal investigator, University Hospital, Antwerp
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00493194
- Sponsor's protocol ID
- 2004-004115-38
- Other IDs
- 2004
- Status last verified
- Oct 2005
- First submitted
- 27 Jun 2007
- Last updated
- 26 Nov 2008
- Results posted
- No
Publications
Flechner SM, Goldfarb D, Modlin C, Feng J, Krishnamurthi V, Mastroianni B, Savas K, Cook DJ, Novick AC. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation. 2002 Oct 27;74(8):1070-6. doi: 10.1097/00007890-200210270-00002.
PubMed 12438948Groth CG, Backman L, Morales JM, Calne R, Kreis H, Lang P, Touraine JL, Claesson K, Campistol JM, Durand D, Wramner L, Brattstrom C, Charpentier B. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation. 1999 Apr 15;67(7):1036-42. doi: 10.1097/00007890-199904150-00017.
PubMed 10221490Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, Berthoux FC, Brattstrom C, Lebranchu Y, Vialtel P. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000 Apr 15;69(7):1252-60. doi: 10.1097/00007890-200004150-00009.
PubMed 10798738Grimm PC, Nickerson P, Gough J, McKenna R, Stern E, Jeffery J, Rush DN. Computerized image analysis of Sirius Red-stained renal allograft biopsies as a surrogate marker to predict long-term allograft function. J Am Soc Nephrol. 2003 Jun;14(6):1662-8. doi: 10.1097/01.asn.0000066143.02832.5e.
PubMed 12761269
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Interstitial Fibrosis in Protocol Biopsies of Renal Allografts: A Prospective, Randomised Trial of Sirolimus Versus Cyclosporine.(Fibrasic)
- ClinicalTrials.gov ID
- NCT00493194
- Acronym / sponsor ID
- 2004-004115-38
- Keywords
- Cyclosporine toxicity, Interstitial Fibrosis, Chronic allograft nephropathy, Sirolimus
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University Hospital, AntwerpUniversity, hospital or other
- Collaborators
- Wyeth is now a wholly owned subsidiary of Pfizer, Hoffmann-La Roche
- Study start
- May 2005
- Study completion
- Jul 2007 (estimated)
- First posted
- 28 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Recipients of a renal allograft, with a minimum age of 18 years.
- Male or female recipients. Women of child-bearing age must practice adequate contraception
- For renal allografts from living donors, at least one HLA-mismatch is required.
- Written informed consent, compliant with local regulations.
Key exclusion criteria (13 listed)
- Recipients of a second or third renal allograft, with a past history of graft failure due to rejection.
- Recipients of a renal allograft from a haplotype-identical living donor or a non-heart beating donor.
- Cold ischemia time > 24 hours
- Recipients of a kidney from donors ≥ 65 years of age
- Recipients of multiple organs.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| sirolimus | Drug | – |
| cyclosporine | Drug | – |
| daclizumab | Drug | – |
Primary outcome
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,
17 secondary outcomes
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.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2008.
- Results publication: PubMed 12438948Flechner SM, Goldfarb D, Modlin C, Feng J, Krishnamurthi V, Mastroianni B, Savas K, Cook DJ, Novick AC. Kidney transplantation without calcineurin inhibitor drugs: a prospective, randomized trial of sirolimus versus cyclosporine. Transplantation. 2002 Oct 27;74(8):1070-6. doi: 10.1097/00007890-200210270-00002.
- Results publication: PubMed 10221490Groth CG, Backman L, Morales JM, Calne R, Kreis H, Lang P, Touraine JL, Claesson K, Campistol JM, Durand D, Wramner L, Brattstrom C, Charpentier B. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation. 1999 Apr 15;67(7):1036-42. doi: 10.1097/00007890-199904150-00017.
- Results publication: PubMed 10798738Kreis H, Cisterne JM, Land W, Wramner L, Squifflet JP, Abramowicz D, Campistol JM, Morales JM, Grinyo JM, Mourad G, Berthoux FC, Brattstrom C, Lebranchu Y, Vialtel P. Sirolimus in association with mycophenolate mofetil induction for the prevention of acute graft rejection in renal allograft recipients. Transplantation. 2000 Apr 15;69(7):1252-60. doi: 10.1097/00007890-200004150-00009.
- Results publication: PubMed 12761269Grimm PC, Nickerson P, Gough J, McKenna R, Stern E, Jeffery J, Rush DN. Computerized image analysis of Sirius Red-stained renal allograft biopsies as a surrogate marker to predict long-term allograft function. J Am Soc Nephrol. 2003 Jun;14(6):1662-8. doi: 10.1097/01.asn.0000066143.02832.5e.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Louis Bosmans, M.D. Ph.D. principal investigator
University Hospital, Antwerp
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing sirolimus, cyclosporine and daclizumab in people with Kidney Failure, Chronic and Transplantation, run by University Hospital, Antwerp at 3 sites in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Nov 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean-Louis Bosmans, MD Ph.D (..32/3/821 37 92, JeanLouis.Bosmans@ua.ac.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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,. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00493194, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2008.