Renal function at two years in liver transplant patients receiving everolimus: results of a randomized, multicenter study.
Saliba F, De Simone P, et al.American Journal of Transplantation 2013; 13(7):1734-45
Aims
To investigate the outcomes of everolimus and reduced tacrolimus on renal function in liver transplant recipients.
Interventions
Participants were randomized into groups that received either everolimus and reduced tacrolimus (tacrolimus trough concentration of 3–5 ng/mL by week 3), tacrolimus control (target tacrolimus trough concentration of8–12 ng/mL until month 4 posttransplant and 6–10 ng/mL thereafter) or tacrolimus elimination (to be completed by the end of month 4). However the study protocol was amended to stop recruitment to the tacrolimus elimination arm and the eligible patients were randomized between the remaining groups.
Participants
719 recipients of a primary full sized liver transplant from a deceased donor who had received tacrolimus and corticosteroids.
Outcomes
The primary outcomes included the composite efficacy failure rate of treated biopsy proven acute rejection, graft loss, or death since randomization. The secondary outcomes included the change in renal function from randomization.
Follow-up
24 months.
CET Conclusions
Enrolment into the Tacrolimus elimination arm of this study was discontinued due to high rates of acute rejection. The other two arms continued to recruit to completion. The composite efficacy failure rate was higher in the standard Tacrolimus arm than the Everolimus+reduced Tacrolimus arm up to 24 months follow up (12.5% versus 10.3%). This difference was accounted for by a higher rate of acute rejection in the standard Tacrolimus arm. The standard Tacrolimus arm also had worse eGFR up to 24 months follow up; the difference in mean eGFR was approximately 7ml/min. The Everolimus+reduced Tacrolimus arm was associated with higher rates of hyperlipidaemia, peripheral oedema and stomatitis.
Data analysis
Modified intention-to-treat analysis
Trial registration
ClinicalTrials.gov - NCT00622869