The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation

TY - JOUR

T1 - The MANDELA study: A multicenter, randomized, open-label, parallel group trial to refine the use of everolimus after heart transplantation

AU - Deuse, Tobias

AU - Bara, Christoph

AU - Barten, Markus J

AU - Hirt, Stephan W

AU - Doesch, Andreas O

AU - Knosalla, Christoph

AU - Grinninger, Carola

AU - Stypmann, Jörg

AU - Garbade, Jens

AU - Wimmer, Peter

AU - May, Christoph

AU - Porstner, Martina

AU - Schulz, Uwe

N1 - Copyright © 2015 Elsevier Inc. All rights reserved.

PY - 2015/11

Y1 - 2015/11

N2 - In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

AB - In recent years a series of trials has sought to define the optimal protocol for everolimus-based immunosuppression in heart transplantation, with the goal of minimizing exposure to calcineurin inhibitors (CNIs) and harnessing the non-immunosuppressive benefits of everolimus. Randomized studies have demonstrated that immunosuppressive potency can be maintained in heart transplant patients receiving everolimus despite marked CNI reduction, although very early CNI withdrawal may be inadvisable. A potential renal advantage has been shown for everolimus, but the optimal time for conversion and the adequate reduction in CNI exposure remain to be defined. Other reasons for use of everolimus include a substantial reduction in the risk of cytomegalovirus infection, and evidence for inhibition of cardiac allograft vasculopathy, a major cause of graft loss. The ongoing MANDELA study is a 12-month multicenter, randomized, open-label, parallel-group study in which efficacy, renal function and safety are compared in approximately 200 heart transplant patients. Patients receive CNI therapy, steroids and everolimus or mycophenolic acid during months 3 to 6 post-transplant, and are then randomized at month 6 post-transplant (i) to convert to CNI-free immunosuppression with everolimus and mycophenolic acid or (ii) to continue reduced-exposure CNI, with concomitant everolimus. Patients are then followed to month 18 post-transplant The rationale and expectations for the trial and its methodology are described herein.

KW - Adrenal Cortex Hormones/administration & dosage

KW - Calcineurin Inhibitors/administration & dosage

KW - Cytomegalovirus Infections/epidemiology

KW - Dose-Response Relationship, Drug

KW - Drug Therapy, Combination

KW - Everolimus/administration & dosage

KW - Graft Rejection/prevention & control

KW - Heart Transplantation/methods

KW - Humans

KW - Immunosuppressive Agents/administration & dosage

KW - Kidney Diseases/chemically induced

KW - Mycophenolic Acid/administration & dosage

KW - Research Design

U2 - 10.1016/j.cct.2015.09.009

DO - 10.1016/j.cct.2015.09.009

M3 - SCORING: Journal article

C2 - 26363128

VL - 45

SP - 356

EP - 363

JO - CONTEMP CLIN TRIALS

JF - CONTEMP CLIN TRIALS

SN - 1551-7144

IS - Pt B

ER -