Scandinavian Heart Transplant Everolimus De Novo Study with Early Calcineurin Inhibitor Avoidance (SCHEDULE)

Abstract

Purpose Calcineurin inhibitors (CNIs) remain the mainstay of immunosuppression following heart transplantation (HTx) but are associated with significant complications such as nephrotoxicity. We therefore designed a randomized trial to assess whether early introduction of everolimus (Evr) followed by withdrawal of cyclosporine (CsA) would lead to superior renal function and less chronic allograft vasculopathy (CAV) in de novo HTx recipients compared to a standard protocol of CsA-based immunosuppression. Methods and Materials A 12 months’ prospective, multicenter, parallell group, open-labeled study with randomization within 5 days post-HTx to CsA, mycophenolate mofetil (MMF) and corticosteroids (CS) (Group A) or to low dose Evr and reduced dose CsA, MMF and CS, with CsA withdrawal and full-dose Evr after 7-11 weeks (Group B). Results The primary objective was to compare renal function assessed by measured glomerual filtration rate (mGFR) 12 months after HTx. Secondary objectives included differences in progression of CAV assessed by IVUS, renal function evaluated by change of mGFR between weeks 7-11 to month 12, renal function estimated by calculated GFR (cGFR) at each follow-up visit, number of rejections and occurence of treatment failures up to 12 months (graft loss, death, loss to follw-up or discontinuation due to lack of efficacy or toxicity), proteinuria, lipid profile, left ventricular function, safety and tolerability). Altogether 116 patients were recruited and randomized to Group A (n = 59) and Group B (n = 57) with mean (SD) age of 51.5 (12.4) and 51.1 (12.8), respectively, from 1. of December 2009 to 31. of December 2011. The last patient will complete the study in December 2012. Conclusions To be presented at the meeting.