| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | American Journal of Transplantation | ||||
| Publisher: | WILEY | ||||
| Place of Publication: | HOBOKEN | ||||
| Volume: | 19 | ||||
| Number of Issue or Book Chapter: | 11 | ||||
| Page Range: | pp. 3006-3017 | ||||
| Date: | 2019 | ||||
| Institutions: | Medicine > Lehrstuhl für Herz-, Thorax- und herznahe Gefäßchirurgie | ||||
| Identification Number: |
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| 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 | ||||
| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 48099 |
Web of ScienceAbstract
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 ...
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.
Metadata last modified: 03 Sep 2021 09:34
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