Barten, Markus J. and Hirt, Stephan W. and Garbade, Jens and Bara, Christoph and Doesch, Andreas O. and Knosalla, Christoph and Grinninger, Carola and Stypmann, Joerg and Sieder, Christian and Lehmkuhl, Hans B. and Porstner, Martina and 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. AMERICAN JOURNAL OF TRANSPLANTATION, 19 (11). pp. 3006-3017. ISSN 1600-6135, 1600-6143
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CARDIAC ALLOGRAFT VASCULOPATHY; LEFT-VENTRICULAR MASS; KIDNEY-TRANSPLANTATION; MULTICENTER; RECIPIENTS; SIROLIMUS; THERAPY; CYCLOSPORINE; FORMULATION; PREDICTION; clinical research; practice; everolimus; heart transplantation; cardiology; immunosuppressant-calcineurin inhibitor (CNI); immunosuppressant-mechanistic target of rapamycin (mTOR); immunosuppression; immune modulation; tacrolimus |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Mar 2020 11:08 |
| Last Modified: | 25 Mar 2020 11:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25939 |
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