Do patient characteristics influence efficacy and renal outcomes in liver transplant patients receiving everolimus?
De Simone P, Saliba F, et al.Clinical Transplantation 2016; 30(3):279-88
Aims
To evaluate the influence of variables that could potentially affect the risk of graft rejection or renal function after liver transplantation.
Interventions
All participants received tacrolimus and corticosteroids, with or without mycophenolic acid (MPA) until day 30, at which point they were randomized to one of three regimens, either everolimus and reduced tacrolimus (EVR+Reduced TAC), TAC Control or TAC Elimination.
Participants
719 adult recipients of a primary full-size liver transplant from a deceased donor who had received tacrolimus and corticosteroids from time of transplant, aged 18–70 years.
Outcomes
Primary outcomes measured were recipient age group, gender, end-stage disease, hepatitis C virus (HCV) status, Model for End-stage Liver Disease (MELD) score, and estimated GFR. Secondary outcomes were treated biopsy-proven acute rejection, risk of graft loss or death and adverse events
Follow-up
24 months
CET Conclusions
The H2304 study was a 24-month prospective randomised multi-centre study of some 700 de novo liver transplant recipients which took place between 2008 and 2012. Adult recipients were randomised to receive Tacrolimus and steroids with or without MPA and after a run-in period were randomised to receive Everolimus and reduced-dose Tacrolimus or continue on standard dose Tacrolimus. This trial was designed to test if a protocol with reduced Tacrolimus would lead to better renal function bearing in mind that chronic kidney disease is a major problem after liver transplantation and is attributed mainly to the calcineurin inhibitors. There was no difference in biopsy proven acute rejection up to two years but the estimated GFR was improved in the Everolimus plus reduced Tac patients. Although the improvement in GFR was seen throughout the study the benefit was seen most in certain subpopulations such as those with a low base-line GFR and those younger recipients (less than 60 years of age), female patients and HCV negative patients. The efficacy of Everolimus and reduced Tacrolimus was maintained for at least two years after liver transplantation even in patients with risk factors for rejection.
Data analysis
Modified intention-to-treat analysis
Trial registration
Clinicaltrials.gov - NCT00622869