Minimizing Immunosuppression in Old for Old Kidney Transplantation

NCT ID: NCT00912678

Last Updated: 2009-06-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-03-31
• Study Completion Date: 2008-10-31

Brief Summary

Kidney transplantation in the elderly is a challenge since patient's co-morbidity and the decreased injury threshold of older grafts may limit the benefits of transplantation in these patients. To compare favourable effects between low dose tacrolimus (LD-Tac) and mycophenolate-mofetil (MMF) in this patient population the investigators conducted a one year prospective multicenter randomized controlled trial. 90 kidney transplant recipients > 65 years with cadaveric grafts (> 65 years) from 5 centers were enrolled and received baseline immunosuppression with daclizumab induction (1 mg/kg) at day one and day 14, LD-Tac (trough level 5-8 µg/ml), MMF (1-2 g/d) and steroids. After three months, patients were centrally randomized either to MMF (1-2 g/d) and steroids (23 patients) or to LD-Tac and steroids. Follow-up visits were performed every 4 weeks up to one year. Protocol biopsies were performed after one year. The investigators' primary hypothesis is that the biopsy proven rejection rate in the MMF group is not significantly different compared to the LD-Tac group after one year. The investigators' secondary hypothesis is that graft function in the MMF group (reflected by the glomerular filtration rate and protocol biopsy result) is superior to the graft function in the LD-Tac group.

Conditions

Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MMF and Steroid Group

Group of Patients randomized to MMF and Steroid maintenance immunosuppression after 3 months (Tacrolimus withdrawal)

Group Type: ACTIVE_COMPARATOR

MMF (Cellcept) and Steroids

Intervention Type: DRUG

Prograf was withdrawn completely after randomization, MMF and steroids were given.

Low-Dose Tacrolimus Group

Patients randomized to withdrawal of MMF after 3 months and maintenance immunosuppression with low-dose tacrolimus and Steroids

Group Type: ACTIVE_COMPARATOR

Tacrolimus (Prograf)

Intervention Type: DRUG

After randomization CellCept was withdrawn completely, low-dose tacrolimus was given.

Interventions

MMF (Cellcept) and Steroids

Prograf was withdrawn completely after randomization, MMF and steroids were given.

Intervention Type: DRUG

Tacrolimus (Prograf)

After randomization CellCept was withdrawn completely, low-dose tacrolimus was given.

Intervention Type: DRUG

Other Intervention Names

Prograf; CellCept; Prograf

Eligibility Criteria

Inclusion Criteria

• Patients receiving a cadaveric kidney transplant (first or re-transplant)
• Patients must met the criteria of the EUROTRANSPLANT program
• Organ allocation with the framework of EUROPEAN SENIOR PROGRAM (ESP) by EUROTRANSPLANT
• Written consent

• Cadaveric kidney from "non heart beating donors"
• One or more than one steroid resistant acute rejections within the first 3 weeks after transplantation
• Two or more than two steroid sensitive rejections (more than 2 administered steroid boli) within the first 3 weeks after transplantation
• Tacrolimus trough level > 10ng/ml in three consecutive measurements
• Allergy against macrolide antibiotics or tacrolimus
• Systemic steroid therapy at study entry not related to transplantation
• History of Malignancy
• Clinical relevant uncontrolled infections, heavy diarrhea, vomiting or active ulcer disease
• Patients who are enrolled in other clinical studies or were enrolled in other clinical studies 28 days before transplantation
• Patients under medication not approved by the German Ministry of Health

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma GmbH

INDUSTRY

Sponsor Role: collaborator

University of Luebeck

OTHER

Sponsor Role: lead

Responsible Party

University of Luebeck Medical School, Medical Clinic I, Transplant Center

Principal Investigators

Lutz Fricke, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Luebeck

Locations

Transplant Center Cologne (Koeln-Mehrheim)

Cologne, Cologne, Germany

University of Essen - Transplant Center

Essen, Hesse, Germany

Charite- Transplant Center - Campus Mitte

Berlin, State of Berlin, Germany

Charite - Transplant Center - Virchow Clinic

Berlin, State of Berlin, Germany

University of Luebeck, Transplant Center

Lübeck, , Germany

Countries

Germany

References

Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, Neylan J, Wilkinson A, Ekberg H, Gaston R, Backman L, Burdick J. Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation. Daclizumab Triple Therapy Study Group. N Engl J Med. 1998 Jan 15;338(3):161-5. doi: 10.1056/NEJM199801153380304.

Reference Type: BACKGROUND

PMID: 9428817 (View on PubMed)

Ducloux D, Motte G, Billerey C, Bresson-Vautrin C, Vautrin P, Rebibou JM, Saint-Hillier Y, Chalopin JM. Cyclosporin withdrawal with concomitant conversion from azathioprine to mycophenolate mofetil in renal transplant recipients with chronic allograft nephropathy: a 2-year follow-up. Transpl Int. 2002 Sep;15(8):387-92. doi: 10.1007/s00147-002-0403-3. Epub 2002 Aug 21.

Reference Type: BACKGROUND

PMID: 12221456 (View on PubMed)

Friemann S, Feuring E, Padberg W, Ernst W. Improvement of nephrotoxicity, hypertension, and lipid metabolism after conversion of kidney transplant recipients from cyclosporine to tacrolimus. Transplant Proc. 1998 Jun;30(4):1240-2. doi: 10.1016/s0041-1345(98)00226-7. No abstract available.

Reference Type: BACKGROUND

PMID: 9636504 (View on PubMed)

Pohanka E, Bechstein WO, Berlakovich G, Binet I, Friemann S, Heemann U, Kliem V, Sperschneider H, Stangl M, Ringe B. [Dosage and monitoring of tacrolimus after kidney transplantation]. Dtsch Med Wochenschr. 2000 May 12;125(19):608-11. No abstract available. German.

Reference Type: BACKGROUND

PMID: 11320722 (View on PubMed)

Other Identifiers

ESP-2004-1

Identifier Type: -

Identifier Source: org_study_id