Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Surgery, Transplantation, REDUCED-DOSE TACROLIMUS, calcineurin inhibitor, clinical research/practice, clinical trial, glomerular filtration rate (GFR), immunosuppressant, immunosuppression/immune modulation, liver allograft function/dysfunction, liver transplantation/hepatology, liver transplantation: split, tacrolimus, Female, Follow-Up Studies, Glomerular Filtration Rate, Graft Rejection, Graft Survival, Humans, Immunosuppressive Agents, Kidney Function Tests, Liver, Liver Diseases, Liver Transplantation, Male, Middle Aged, Postoperative Complications, Prognosis, Risk Factors, Tacrolimus, DIAMOND† study group, 11 Medical and Health Sciences, 3202 Clinical sciences, 3204 Immunology

Abstract:

multicenter, 24-week, randomized trial investigating the effect of different once-daily, prolonged-release tacrolimus dosing regimens on renal function after de novo liver transplantation. Arm 1: prolonged-release tacrolimus (initial dose 0.2mg/kg/day); Arm 2: prolonged-release tacrolimus (0.15-0.175mg/kg/day) plus basiliximab; Arm 3: prolonged-release tacrolimus (0.2mg/kg/day delayed until Day 5) plus basiliximab. All patients received MMF plus a bolus of corticosteroid (no maintenance steroids). Primary endpoint: eGFR (MDRD4) at Week 24. Secondary endpoints: composite efficacy failure, BCAR and AEs. Baseline characteristics were comparable. Tacrolimus trough levels were readily achieved posttransplant; initially lower in Arm 2 versus 1 with delayed initiation in Arm 3. eGFR (MDRD4) was higher in Arms 2 and 3 versus 1 (p = 0.001, p = 0.047). Kaplan-Meier estimates of composite efficacy failure-free survival were 72.0%, 77.6%, 73.9% in Arms 1-3. BCAR incidence was significantly lower in Arm 2 versus 1 and 3 (p = 0.016, p = 0.039). AEs were comparable. Prolonged-release tacrolimus (0.15-0.175mg/kg/day) immediately posttransplant plus basiliximab and MMF (without maintenance corticosteroids) was associated with lower tacrolimus exposure, and significantly reduced renal function impairment and BCAR incidence versus prolonged-release tacrolimus (0.2mg/kg/day) administered immediately posttransplant. Delayed higher-dose prolonged-release tacrolimus initiation significantly reduced renal function impairment compared with immediate posttransplant administration, but BCAR incidence was comparable.