Everolimus versus mycophenolate mofetil de novo after lung transplantation - a prospective, randomized, open-label trial.
Strueber M, Warnecke G, et al.American journal of transplantation 2016; [record in progress].
Aims
To compare the efficacy and safety of everolimus and mycophenolate mofetil (MMF) in combination with cyclosporine A (CsA) and prednisolone as immunosuppressive treatment for de novo lung transplant recipients.
Interventions
All participants were on triple drug immunosuppression according to the center’s protocol using CsA, MMF and steroids. Participants were randomized on post-transplant day 28 to either maintain the current immunosuppressive regimen (control group), or to have MMF replaced by Everolimus combined with a lowered CsA dose (Everolimus group).
Participants
190 male or non-pregnant female recipients of de novo single or double lung transplantation aged 18-65 years.
Outcomes
The primary outcome measured was the incidence of bronchiolitis obliterans syndrome. Secondary measured outcomes included acute rejection, infections and renal function.
Follow-up
2 years
CET Conclusions
In this RCT de novo single or double lung transplant recipients were randomised to conversion to everolimus at 28 days posttransplant or continuation of triple therapy of MMF, CsA and steroids. The primary endpoint was bronchiolitis obliterans syndrome (BOS) which was reviewed both locally and by two blinded, independent experts. The sample size calculation was based on BOS and showed that 190 patients were needed to provide 80% power. Of the 190 participants only half completed the 2-year on drug treatment. Intention to treat analysis showed no difference between groups for BOS although a difference was shown for the per protocol analysis. In 97% of cases there was agreement between the local and blinded reviewers however the reviewers only agreed in 64% of cases on the date of BOS onset. The reliability of the results is limited by the overall high discontinuation rate, which was higher in the everolimus group compared with the CsA group (55% versus 43%). The generalisability of the results is limited by the exclusion of patients with recurrent rejection or patients who had severe primary non-function in the immediate posttransplant period.
Data analysis
Strict intention-to-treat analysis
Trial registration
Clinicaltrials.gov - NCT00402532