Clinical trial NCT01002339
Conditions: Diabetes Mellitus, Adult-Onset
Sponsor: Armando Torres Ramírez
Start date: 2010-02-01; Completion date: 2015-06-01
Enrollment: 134 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. Cyclosporine (CsA) and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, Tacrolimus increases 2 times the risk of NODAT as compared to CsA.

Detailed description:
New onset diabetes after renal transplantation (NODAT) is a common and severe complication negatively influencing graft and patient survival. CsA and Tacrolimus are the basis of modern immunosuppression. Tacrolimus is superior to CsA in terms of acute rejection and graft function. However, increases 2 times the risk of NODAT as compared to CsA. Objectives: a) To compare the incidence of NODAT and glucose intolerance with 3 different regimes: Tacrolimus with rapid steroid withdrawal; Tacrolimus with steroids minimization; and CsA with steroid minimization; b) To compare acute rejection rate, renal function and graft and patient survival between different regimes; and c) to investigate the influence of different regimes on subclinical atheromatosis. A total of 210 patients will be randomized. The primary efficacy variable will be NODAT or glucose intolerance at 1 year; secondary efficacy variables will be acute rejection, renal function, and changes of carotid intima-media thickness over time.

Arms: arm 1: Basiliximab induction. Tacrolimus plus Mycophenolate mofetil (MMF), and corticosteroids with rapid withdrawal after one week. arm 2: Basiliximab induction.Tacrolimus plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal arm 3: Basiliximab induction. Ciclosporin A (CsA) plus Mycophenolate mofetil (MMF) and low-dose corticosteroids for 6 months with subsequent removal
Interventions: intervention 1: Tacrolimus with rapid steroid withdrawal intervention 2: Tacrolimus with steroids minimization intervention 3: CsA with steroid minimization
Intervention descriptions: intervention 1: * Basiliximab induction (4 mg i.v., days 0 and 4).
* Corticosteroids: 0.5 gr of i.v. Methylprednisolone (MP) intraoperatively and 125 mg on the first day, followed by oral doses of prednisone rapidly tapered from 30 mg/day to complete discontinuation by postoperative day 7.
* Tacrolimus: 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month and then 5-8 ng/ml.
* Mycophenolate mofetil 1 gr b.i.d. for the first month and then 500 mg b.i.d. intervention 2: * Basiliximab induction (4 mg i.v., days 0 an 4)
* Corticosteroids: 0.5 gr of i.v. MP intraoperatively and 60 mg on the first day, followed by oral doses of prednisone starting with 0.3 mg/Kg/day, and gradual weekly tapering to complete discontinuation over 6 months.
* Tacrolimus 0.15 mg/Kg/day to achieve target trough levels of 8-12 ng/ml for the first month and then 5-8 ng/ml.
* Mycophenolate mofetil 1 gr b.i.d. for the first month and then 500 mg b.i.d. intervention 3: * Basiliximab induction (4 mg i.v., days 0 an 4)
* Corticosteroids: 0.5 gr of i.v. MP intraoperatively and 60 mg on the first day, followed by oral doses of prednisone starting with 0.3 mg/Kg/day, and gradual weekly tapering to complete discontinuation over 6 months.
* CsA 5 mg/Kg/day to achieve target trough of 150-200 ng/ml the first month and then 100-150 ng/ml.
* Mycophenolate mofetil 1 gr b.i.d

Protocol documents: