81 Early vs. Delayed EVERolimus in De Novo HEART Transplant Recipients

Purpose Multicenter clinical trials showed that everolimus (EVE) associated with low dose cyclosporine (CSA) is superior to azathioprine and equivalent to mycophenolate (MMF) in preventing myocardial acute rejection in de novo heart recipients. In addition, data from randomized and non-randomized studies suggest that EVE may have ancillary properties that may favorably impact long-term survival, by reducing the progression of allograft vasculopathy, the incidence of cytomegalovirus infection, and the onset of post-transplant malignancies. Nonetheless, EVE safety profile still needs to be optimized in particular in the early post-surgery phase, because of a worsening renal function when used with full-dose CSA, and because EVE anti-proliferative properties may delay surgical wound healing and increase the risk for pleural and pericardial effusions. The purpose of this 6-month, controlled, randomized study in de novo heart transplant patients is to compare the occurrence of a composite safety enpoint between a strategy based on delayed introduction of EVE – with MMF as a 4 to 6 weeks bridge in the post-transplant period – and EVE started within post-operative day 5. EVE start dose is adjusted according with some patients' characteristics potentially associated with EVE-related adverse events. This study is sponsored by Novartis Farma Italy and is registered at clinicaltrials.gov ( NCT 01017029 ). Methods and Materials The primary study enpoint is the 6-month composite cumulative incidence of wound healing complications related to initial transplant surgery, pleural/pericardial effusions and occurrence of acute renal insufficiency, defined as GFR ≤ 30/ml/min/1.73m 2 . Results This study has been designed to compare the safety of two EVE strategies of administration that differ from what has been tested in the clinical trials conducted since now. Thus, for patients safety purposes, in the study design we anticipated a pre-specified interim analysis when at least 60 randomized patients completed the first 3-months of follow-up. Conclusions The interim analysis will be completed in January 2011.