Clinical trial NCT00912678: Minimizing Immunosuppression in Old for Old Kidney Transplantation
Official title: Prospective Randomized Controlled Trial to Compare a Calcineurin Inhibitor Free Immunosuppression With a Low Dose Tacrolimus Based Immunosuppression in "Old for Old" Kidney Transplantation.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Keywords: Kidney transplantation
Old for old kidney transplantation
European senior program
Calcineurin inhibitor free immunosuppression
Lead sponsor: University of Luebeck
Sponsor class: OTHER
Collaborators: name: Astellas Pharma GmbH
First posted: 2009-06-03
Enrollment: 90
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Exclusion Criteria:

* Not fulfilled inclusion criteria
* 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

Primary outcomes:
measure: Acute rejection rate
timeFrame: One year
Secondary outcomes:
measure: Graft function
timeFrame: One year
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite- Transplant Center - Campus Mitte
city: Berlin
country: Germany
facility: Charite - Transplant Center - Virchow Clinic
city: Cologne
country: Germany
facility: Transplant Center Cologne (Koeln-Mehrheim)
city: Essen
country: Germany
facility: University of Essen - Transplant Center
city: Luebeck
country: Germany
facility: University of Luebeck, Transplant Center
Study officials:
affiliation: University of Luebeck
name: Lutz Fricke, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.