In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30+/-5 days post-transplant to start everolimus+reduced tacrolimus (EVR+rTAC)
or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months post-transplant: difference -0.7% [90%CI -5.2%, 3.7%]; p<0.001 for non-inferiority. tBPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated GFR from randomization to month 12, achieved non-inferiority (p<0.001 for non-inferiority), but not superiority and was similar between groups overall (mean -8.0 versus -12.1mL/min/1.73m2 ,p=0.108), and in patients continuing
Reviewer: Centre for Evidence in Transplantation
This non-inferiority, open-label, multicentre, RCT of 284 adult living donor liver transplantation compared everolimus plus reduced tacrolimus with standard tacrolimus. Recipients of a primary orthotopic liver graft from a living donor with adequate graft function were recruited from 38 centres in Asia, North-America and Europe and randomised 1 month post-transplant using concealed allocation. The initial sample size calculation required 470
Aims : To report 12 month results of the ongoing randomized study (H2307) and demonstrate the efficacy and safety between everolimus (EVR) with reduced tacrolimus (rTAC) versus standard tacrolimus (TAC).
Interventions : Participants were randomised at 30±5 days post-transplant to receive either EVR+rTAC or continue with standard TAC.
Participants : 284 recipients of a primary orthotopic liver allograft from a living-donor, aged ≥18 years who had been initiated on a protocol-defined TAC based immunosuppressive regimen.
Outcomes : The primary outcome measured was a composite of efficacy failure which included treated biopsy proven acute rejection (tBPAR), graft loss, or death. Secondary outcomes included the change in estimated GFR, incidence and severity of tBPAR, BPAR and treated acute rejection, urinary protein/creatinine ratio, incidence of proteinuria and renal replacement therapy, rate of HCC recurrence, and safety outcomes including adverse events and laboratory values.
Follow up : 12 months