Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial.
Eisen HJ, Kobashigawa J, et al.American Journal of Transplantation 2013; 13(5):1203-16
Aims
To investigate the non-inferiority of everolimus to mycophenolate mofetil in de novo heart transplant patients.
Interventions
Patients received either 1.5mg everolimus (target trough concentration 3-8ng/mL) with reduced cyclosporine, everolimus 3.0mg (target trough concentration 6-12ng/mL) with reduced cyclosporine or MMF 3g (1.5mg b.i.d) with full dose cyclosporine. Corticosteroids were administered according to local practice.
Participants
721 de novo heart transplant recipients aged 18-70 years.
Outcomes
The primary outcomes included: the composite incidence of biopsy proven acute rejection, acute rejection associated with hemodynamic compromise, graft loss, retransplantation, death or loss to follow-up at 12 months posttransplant.
Follow-up
24 months.
CET Conclusions
Enrolment in one arm of this 3-arm study, everolimus 3mg, was halted early on recommendation of the Data Monitoring Committee due to a higher mortality rate. The immunosuppression profiles in the 2 remaining arms were different in that not only was the study drug different but Cyclosporine dosing was also different (reduced-dose versus full dose). Antibody induction was at the discretion of individual centres. Everolimus 1.5mg was non-inferior for the composite primary outcome of acute rejection, graft loss or death. Renal function at 12 and 24 months was slightly worse in the everolimus 1.5mg arm than the MMF arm. The incidence of non-fatal adverse events was higher in the everolimus 1.5mg arm. CMV infections were higher in the MMF arm. Everolimus 1.5mg was associated with a smaller increase in maximum initial thickness on intravascular ultrasound. The incidence of study medication discontinuation was higher in the everolimus arm. These results cannot necessarily be extrapolated to regimens which include tacrolimus.
Data analysis
Per protocol analysis
Trial registration
ClinicalTrials.gov – NCT00300274