Everolimus With Reduced Tacrolimus Improves Renal Function in De Novo Liver Transplant Recipients: A Randomized Controlled Trial.
De Simone P, Nevens F, et al.American Journal of Transplantation [record in progress].
Aims
To evaluate the efficacy and safety of everolimus with eliminated or reduced tacrolimus compared with a standard tacrolimus regimen in de novo liver transplant recipients.
Interventions
Everolimus with tacrolimus elimination (TAC elimination) versus everolimus with reduced-exposure tacrolimus (EVR+TAC reduced) or standard-exposure tacrolimus (TAC control). All patients received steroids.
Participants
719 de novo liver transplant patients.
Outcomes
The primary efficacy endpoint was the composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss or death at 12 months posttransplantation. The main secondary endpoint was renal function assessed by estimated glomerular filtration rate. Safety assessment included adverse events, serious adverse events, wound healing complications and incidence of infections.
Follow-up
12 months
CET Conclusions
In this multicentre trial in first liver transplant patients there were 3 arms but those randomised to tacrolimus elimination had a much higher rate of biopsy proven acute rejection and that arm of the trial was discontinued prematurely. In the other two arms the combined efficacy end point (biopsy proven rejection, graft survival and patient survival) were superior in the everolimus and reduced tacrolimus arm in comparison to patients on tacrolimus alone. The primary efficacy end point was the combination of biopsy proven acute rejection, graft survival and patient survival at 12 months after randomisation. The authors conclude that using this combined efficacy end point that the everolimus and reduced tacrolimus was non inferior to the TAC control. However it should be noted that drug discontinuation for adverse events was double in the everolimus and reduced TAC arm compared to the TAC controls. Although the authors conclude that everolimus allows early tacrolimus minimisation, with some benefit in terms of better renal function compared to a standard tacrolimus regimen, there is a high rate of adverse events with the use of sirolimus.
Data analysis
Strict intention-to-treat analysis
Trial registration
Not reported