UNLABELLED: DIAMOND: 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.

Abdominal Transplant Surgery University Hospitals Leuven Leuven Belgium

Astellas Pharma Europe Ltd London United Kingdom

Astellas Pharma Inc Northbrook IL

Department of Abdominal Surgery A 5 Vishnevsky Institute of Surgery Moscow Russian Federation

Department of General Visceral and Transplantation Surgery Hannover Medical School Hannover Germany

Department of General Visceral and Transplantation Surgery Westpfalz Klinikum Hospital Kaiserslautern Germany

Department of General Visceral and Vascular Surgery Jena University Hospital Thuringia Germany

Department of Nephrology and Organ Transplantation Toulouse University Hospital Toulouse France

Department of Surgery Goethe University Hospital and Clinics Frankfurt Germany

Department of Transplantation and Liver Surgery Clinic Helsinki University Hospital Helsinki Finland

Liver Transplant Unit Policlinico di Tor Vergata Rome Italy

The Transplant Institute Sahlgrenska University Hospital Gothenburg Sweden

Transplantcentre Institute for Clinical and Experimental Medicine Prague Czech Republic

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