Comparing everolimus-based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from 6 months after heart transplantation: The randomized MANDELA study

Barten, Markus J.; Hirt, Stephan W.; Garbade, Jens; Bara, Christoph; Doesch, Andreas O.; Knosalla, Christoph; Grinninger, Carola; Stypmann, Jörg; Sieder, Christian; Lehmkuhl, Hans B.; Porstner, Martina und Schulz, Uwe (2019): Comparing everolimus-based immunosuppression with reduction or withdrawal of calcineurin inhibitor reduction from 6 months after heart transplantation: The randomized MANDELA study. In: American Journal of Transplantation, Bd. 19, Nr. 11: S. 3006-3017

Abstract

In the 12-month, open-label MANDELA study, patients were randomized at month 6 after heart transplantation to (1) convert to calcineurin inhibitor (CNI)-free immunosuppression with everolimus (EVR), mycophenolic acid and steroids (CNI-free, n = 71), or to (2) continue reduced-exposure CNI, with EVR and steroids (EVR/redCNI, n = 74). Tacrolimus was administered in 48.8% of EVR/redCNI patients and 52.6% of CNI-free patients at randomization. Both strategies improved and stabilized renal function based on the primary endpoint (estimated GFR at month 18 posttransplant postrandomization) with superiority of the CNI-free group vs EVR/redCNI: mean 64.1 mL/min/1.73 m(2) vs 52.9 mL/min/1.73 m(2);difference + 11.3 mL/min/1.73 m(2) (P < .001). By month 18, estimated GFR had increased by >= 10 mL/min/1.73 m(2) in 31.8% and 55.2% of EVR/redCNI and CNI-free patients, respectively, and by >= 25 mL/min/1.73 m(2) in 4.5% and 20.9%. Rates of biopsy-proven acute rejection (BPAR) were 6.8% and 21.1%;all cases were without hemodynamic compromise. BPAR was less frequent with EVR/redCNI vs the CNI-free regimen (P = .015);6 of 15 episodes in CNI-free patients occurred with EVR concentration mL. Rates of adverse events and associated discontinuations were comparable. EVR/redCNI from month 6 achieved stable renal function with infrequent BPAR. One-year renal function can be improved by early conversion to EVR-based CNI-free therapy but requires close EVR monitoring. Clinical trials registry: ClinicalTrials.gov NCT00862979.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 1600-6135
• Sprache: Englisch