Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients
Year: 2017
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: BACKGROUND: Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. METHODS: This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate ≤30/mL/min per 1.73 m) in de novo HTx recipients receiving immediate everolimus (EVR-I) (≤144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection ≥ 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint. RESULTS: Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02). CONCLUSIONS: Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy.
Source: Transplantation
Institutions: IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola, University of Pavia, Policlinico San Matteo Fondazione, Ospedale Monaldi, Ospedale Santa Maria della Misericordia di Udine, Azienda Ospedaliera Universitaria Senese, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, University of Verona, Azienda Ospedaliera San Camillo-Forlanini, Azienda Ospedale - Università Padova, Azienda Ospedaliera G. Brotzu, Fondazione Ricerca Molinette
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W2758802779