Efficacy and safety of everolimus with reduced tacrolimus in living-donor liver transplant recipients: 12-month results of a randomized multicenter study.
Jeng L, Lee SG, et al.American Journal of Transplantation 2017; 13: 13.
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
CET Conclusions
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 patients but due to slow recruitment this was changed to 280 patients by increasing the one-sided α error rate from 2.5% to 5%. The intention-to-treat analysis showed that everolimus plus reduced tacrolimus was non-inferior when compared to standard tacrolimus for the primary composite endpoint of biopsy-proven acute rejection, graft loss or death at 12 months post-transplant. Renal function (eGFR) was significantly better in the everolimus plus reduced tacrolimus until month 6, after which the difference was no longer significant. However, there were more adverse events and (serious) adverse events or infections with suspected relation to the study drug in the everolimus plus reduced tacrolimus group.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT01888432