A randomized embedded multifactorial adaptive platform for extra corporeal membrane oxygenation (REMAP ECMO) - design and rationale of the left ventricular unloading trial domain.

Background: The use of Extracorporeal Membrane Oxygenation (ECMO) remains associated with high rates of complications, weaning failure and mortality which can be partly explained by a knowledge gap on how to properly manage patients on ECMO support. To address relevant patient management issues, we designed a "Randomized Embedded Multifactorial Adaptive Platform (REMAP)" in the setting of ECMO (REMAP ECMO) and a first embedded randomized controlled trial (RCT) investigating the effects of routine early left ventricular (LV) unloading through intra-aortic balloon pumping (IABP).
Methods: REMAP ECMO describes a registry-based platform allowing for the embedding of multiple response adaptive RCTs (trial domains) which can perpetually address the effect of relevant patient management issues on ECMO weaning success. A first trial domain studies the effects of LV unloading by means of an IABP as an adjunct to veno-arterial (V-A) ECMO versus V-A ECMO alone on ECMO weaning success at 30 days in adult cardiogenic shock patients admitted to the Intensive Care Unit (ICU). The primary outcome of this trial is "successful weaning from ECMO" being defined as a composite of survival without the need for mechanical circulatory support, heart transplantation, or left ventricular assist device (LVAD) at 30 days after initiation of ECMO. Secondary outcomes include the need for interventional escalation of LV unloading strategy, mechanistic endpoints, survival characteristics until 1 year after ECMO initiation, and quality of life. Trial data will be analysed using a Bayesian statistical framework. The adaptive design allows for a high degree of flexibility, such as response adaptive randomization and early stopping of the trial for efficacy or futility. The REMAP ECMO LV unloading study is approved by the Medical Ethical Committee of the Erasmus Medical Center and is publicly registered.
Conclusion: This REMAP ECMO trial platform enables the efficient roll-out of multiple RCTs on relevant patient management issues. A first embedded trial domain will compare routine LV unloading by means of an IABP as an adjunct to V-A ECMO versus V-A ECMO alone.
Trial Registration: ClinicalTrials.gov, NCT05913622.
Competing Interests: Conflict of interest Christiaan L. Meuwese: • Received research grants from the Dutch Heart Foundation and Erasmus Medical Center. Dirk W. Donker: • Research cooperation: Getinge-Maquet Critical Care AB, Solna, Sweden Research cooperation: Sonion BV, Hoofddorp, The Netherlands • Research consultancy: HBOX Therapies GmbH, Aachen, Germany • No personal fees received, all financial benefits paid to the University of Twente, Enschede, The Netherlands Rudolf A. de Boer: • Received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals GmbH, Novo Nordisk, and Roche; • Speaker engagements with and/or received fees from and/or served on an advisory board for Abbott, AstraZeneca, Bristol Myers Squibb, Cardior Pharmaceuticals GmbH, NovoNordisk, and Roche; • Received travel support from Abbott, Cardior Pharmaceuticals GmbH, and NovoNordisk. Adriaan O. Kraaijeveld: • Received an institutional research grant van Xenios AG Diederik A.M.P.J. Gommers: •Received speakers fee and travel expenses from: Draeger, GE Healthcare, Maquet and Novalung. •Member of medical advisory board: GE Healthcare (2009-2012), Novalung (2015-2018) Roberto Lorusso • Received research grants from Medtronic and LivaNova • Principle Investigator of the PERSIST AVR Trial (sponsored by LivaNova) • Consultant for Medtronic, LivaNova and Getinge • Member of the Medical Advisory Board for Eurosets and Xenios • Honoraria for moderations or presentations from ABIOMED • Payments to the Institution/University Nicolas M.D.A. Van Mieghem • Received research grant support from: Abbott, Astra Zeneca*, Biotronik, Boston Scientific, CSI, Daiichi Sankyo, Edwards Lifesciences*, Medtronic, Pie Medical, PulseCath BV, Teleflex • Received advisory fees from: 415 Capital Management GmbH, Abbott, Abiomed, Acist Medical, Amgen, Anteris, Approxima Srl, Biotronik, Bolt Medical, Boston Scientific, CSI, Daiichi Sankyo, Jenavalve, LUMA Vision, Materialise, Medtronic, Opsens, Pie Medical, PulseCath BV, Shockwave, Siemens, Springer Healthcare, Teleflex All other authors have no conflicts of interest to declare.
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