Renal Function in De Novo Liver Transplant Recipients Receiving Different Prolonged-Release Tacrolimus Regimens The DIAMOND Study

American Journal of Transplantation. 2015 Jul; 15(7): 1843-54

Aims
To investigate renal function with once daily prolonged-release tacrolimus (advagraf)-based immunosuppression in de novo liver transplant recipients.

Interventions
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.

Participants
857 patients; 289 assigned to prolonged-release tacrolimus (; 291 assigned to prolonged-release tacrolimus plus basiliximab , 277 assigned to delayed introduction of prolonged release tacrolimus plus basiliximab.

Outcomes
Primary endpoint was renal function (eGFR). Secondary endpoints were composite efficacy failure, biopsy confirmed acute rejection and adverse events.

Follow-up
24 weeks

CET Conclusions
The large, non-inferiority DIAMOND trial compared late introduction of prolonged-release tacrolimus versus reduced initial dose prolonged-release tacrolimus, both regimes with mycophenolate mofetil (MMF) and basiliximab, versus prolonged-release tacrolimus plus MMF alone (standard arm). The sample size calculation showed that 900 patients were needed to provide 80% power to detect a difference of 10% in mean eGFR. The primary analysis was on the per protocol population (643 randomised patients who received one dose of the study drug, were transplanted and did not have a major protocol violation) and the full analysis set (844 randomised patients who received one dose of the study drug and were transplanted). 893 patients were randomised and 73% completed the study with the main reason for study discontinuation being adverse events. Using the full analysis set, eGFR was comparable between the late introduction and reduced initial dose of prolonged-release tacrolimus arms and eGFR for these arms was significantly higher than the standard arm at 24 weeks. The reduced initial dose prolonged-release tacrolimus arm showed the lowest incidence of biopsy-confirmed acute rejection compared to two other arms.

Jadad score
3

Data analysis
Modified intention-to-treat analysis

Allocation concealment
Yes

Trial registration
NCT01011205

Funding source
Industry funded