Minimizing Immunosuppression in Old for Old Kidney Transplantation

NCT00912678 | Completed Phase 4 DMC

• 1 other identifier: ESP-2004-1
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 5

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

Keywords

Kidney transplantation; Old for old kidney transplantation; European senior program; Calcineurin inhibitor free immunosuppression

Outcome Measures

Primary Outcomes (1)

• Acute rejection rate

  One year

Secondary Outcomes (1)

• Graft function

  One year

Study Arms (2)

MMF and Steroid Group

ACTIVE COMPARATOR

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

Drug: MMF (Cellcept) and Steroids

Low-Dose Tacrolimus Group

ACTIVE COMPARATOR

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

Drug: Tacrolimus (Prograf)

Interventions

MMF (Cellcept) and Steroids DRUG

Prograf was withdrawn completely after randomization, MMF and steroids were given.

Also known as: Prograf, CellCept

MMF and Steroid Group

Tacrolimus (Prograf) DRUG

After randomization CellCept was withdrawn completely, low-dose tacrolimus was given.

Also known as: Prograf

Low-Dose Tacrolimus Group

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Luebeck: lead
• Astellas Pharma GmbH: collaborator

Study Sites (5)

Transplant Center Cologne (Koeln-Mehrheim)

Cologne, Cologne, 51109, Germany

Location

University of Essen - Transplant Center

Essen, Hesse, Germany

Location

Charite- Transplant Center - Campus Mitte

Berlin, State of Berlin, 10117, Germany

Location

Charite - Transplant Center - Virchow Clinic

Berlin, State of Berlin, 13353, Germany

Location

University of Luebeck, Transplant Center

Lübeck, 23562, Germany

Location

Related Publications (4)

• 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.

  PMID: 9428817 BACKGROUND

• 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.

  PMID: 12221456 BACKGROUND

• 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.

  PMID: 9636504 BACKGROUND

• 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.

  PMID: 11320722 BACKGROUND

MeSH Terms

Interventions

Mycophenolic Acid; Steroids; Tacrolimus

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Fused-Ring Compounds; Polycyclic Compounds; Macrolides; Lactones

Study Officials

• Lutz Fricke, MD, PhD

  University of Luebeck

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 1, 2009
• First Posted: June 3, 2009
• Study Start: March 1, 2002
• Primary Completion: July 1, 2006
• Study Completion: October 1, 2008
• Last Updated: June 3, 2009

Record last verified: 2009-06

Locations

DE (5)