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

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• 作者：Tobias Deuse^a ; ^{t.deuse@uke.de" class="auth_mail" title="E-mail the corresponding author} ; Christoph Bara^b ; ^{bara.christoph@mh-hannover.de" class="auth_mail" title="E-mail the corresponding author} ; Markus J. Barten^a ; ^c ; ^{m.barten@uke.de" class="auth_mail" title="E-mail the corresponding author} ; Stephan W. Hirt^d ; ^{Stephan.Hirt@klinik.uni-regensburg.de" class="auth_mail" title="E-mail the corresponding author} ; Andreas O. Doesch^e ; ^{Andreas.Doesch@med.uni-heidelberg.de" class="auth_mail" title="E-mail the corresponding author} ; Christoph Knosalla^f ; ^{knosalla@dhzb.de" class="auth_mail" title="E-mail the corresponding author} ; Carola Grinninger^g ; ^{Carola.Grinninger@med.uni-muenchen.de" class="auth_mail" title="E-mail the corresponding author} ; Jö ; rg Stypmann^h ; ^{stypmann@ukmuenster.de" class="auth_mail" title="E-mail the corresponding author} ; Jens Garbade^c ; ^{Jens.Garbade@herzzentrum-leipzig.de" class="auth_mail" title="E-mail the corresponding author} ; Peter Wimmerⁱ ; ^{peter.wimmer@novartis.com" class="auth_mail" title="E-mail the corresponding author} ; Christoph Mayⁱ ; ^{christoph.may@novartis.com" class="auth_mail" title="E-mail the corresponding author} ; Martina Porstnerⁱ ; ^{martina.porstner@novartis.com" class="auth_mail" title="E-mail the corresponding author} ; Uwe Schulz^j ; ^{uschulz@hdz-nrw.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BPAR ; biopsy-proven acute rejection ; CAV ; cardiac allograft vasculopathy ; CMV ; cytomegalovirus ; CNI ; calcineurin inhibitor ; CsA ; cyclosporine ; eGFR ; estimated glomerular filtration rate ; IVUS ; intravascular ultrasound ; LVAD ; left ventricular assist device ; MIT ; maximal intimal thickness ; MMF ; mycophenolate mofetil ; mTOR ; mammalian target of rapamycin
• 刊名：Contemporary Clinical Trials
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：45
• 期：part_PB
• 页码：356-363
• 全文大小：517 K

文摘

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.