MANDELA Study Results at 18 Months after Heart Transplantation: Superior renal function with CNI-free everolimus over standard CNI-based regimen- a randomized, multi-center trial in de novo heart transplant recipients. (July 2018) - Barten, Markus J
Abstract : Mandela Study Group. Purpose: The MANDELA study (NCT00862979) was designed to assess the benefit on renal function of either CNI-free or CNI-minimized EVR-based regimen after early conversion of de novo heart transplant recipients (HTxR). Methods: MANDELA is a multi-center, randomized, controlled, open-label, 12 month study. In total 232 de novo HTxR were enrolled 3 months post Tx, of whom 162 could be randomized (1:1) to receive either EVR (C0-h 5-10ng/mL) with reduced CNI (TAC C0-h 3-8ng/mL or CsA C0-h 50-150ng/mL) and steroids (⩽0.3mg/kg) or EVR (C0-h 5-10ng/mL) with mycophenolic acid (EC-MPS max. 2880mg/day or MMF max. 3g/day) and steroids (⩽0.3mg/kg). The primary objective was superiority of cGFR (MDRD) 12 months after randomization for CNI-free over CNI-reduced EVR treatment. Key secondary objectives included efficacy (composite of BPAR ISHLT1990 grade ≥3A/ISHLT2004 grade ≥2R, graft loss/re-transplant, death or loss to follow-up) and assessment of safety profiles including infections. Results: Primary endpoint for superior renal function in CNI-free EVR arm was met with high significance with a difference of +11.2 ml/min in favor of CNI-free EVR arm vs CNI-reduced group (p<0.0001) [cGFR (ml/min) MDRD; LS-mean ANCOVA with LOCF] (Figure 1: course of mean±SD cGFR; MDRD). Per protocol analysis showed a difference of +19.0 ml/min in favor of CNI-free EVR arm (p<0.0001) [cGFR (ml/min) from MDRD formula; LS-mean from ANCOVA model]. Occurrence of MACE and BPAR was in line with international standards and the safety profile was according to the patient population and the treatment compounds investigated herein. Data from full analysis will be available for presentation at TTS-2018 meeting. Conclusion: The MANDELA study showed that improved renal function can be achieved by early conversion to an everolimus based CNI-free regimen in HTxR without compromising safety and efficacy. Hans B Lehmkuhl. Figure. No caption available.