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

American Heart Journal, vol. 279, pp. 81–93

Abstract

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.

Authors 26

1. Myrthe P. J. van Steenwijk

   Erasmus MC

   Affiliation as printed

   Department of Intensive Care, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus Medical Center, Rotterdam, the Netherlands

2. Joost van Rosmalen

   Erasmus MC

   Affiliation as printed

   Departments of Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

3. Carlos V. Elzo Kraemer Aachen Department of Intensive Care

   Leiden University Medical Center

   Affiliation as printed

   Department of Intensive Care, Leiden University Medical Center, Leiden, the Netherlands

4. Dirk Wilhelm Donker

   University Medical Center Utrecht · University of Twente

   Affiliation as printed

   Department of Intensive Care, University Medical Center Utrecht, Utrecht, the Netherlands; Cardiovascular and Respiratory Physiology, University of Twente, Enschede, the Netherlands

5. Jeannine A. J. M. Hermens

   University Medical Center Utrecht

   Affiliation as printed

   Department of Intensive Care, University Medical Center Utrecht, Utrecht, the Netherlands

6. Adriaan O. Kraaijeveld

   University Medical Center Utrecht

   Affiliation as printed

   Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands

7. Jacinta J. Maas Aachen Department of Intensive Care

   Leiden University Medical Center

   Affiliation as printed

   Department of Intensive Care, Leiden University Medical Center, Leiden, the Netherlands

8. Şakir Akın

   Haga Hospital

   Affiliation as printed

   Department of Intensive Care, Haga Hospital, The Hague, the Netherlands

9. Leon J. Montenij

   Catharina Ziekenhuis

   Affiliation as printed

   Department of Intensive Care, Catharina Hospital Eindhoven, Eindhoven, the Netherlands

10. Alexander P. J. Vlaar

    Amsterdam University Medical Centers

    Affiliation as printed

    Department of Intensive Care, Amsterdam University Medical Center, Amsterdam, the Netherlands

11. Walter M. van den Bergh

    University Medical Center Groningen

    Affiliation as printed

    Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands

12. Annemieke Oude Lansink‐Hartgring

    University Medical Center Groningen

    Affiliation as printed

    Department of Critical Care, University Medical Center Groningen, Groningen, the Netherlands

13. Jesse de Metz

    OLVG

    Affiliation as printed

    Department of Intensive Care, OLVG Amsterdam, Amsterdam, the Netherlands

14. Niek Voesten

    Amphia Ziekenhuis

    Affiliation as printed

    Department of Intensive Care, Amphia Hospital Breda, Breda, the Netherlands

15. Eric H. Boersma

    Erasmus MC

    Affiliation as printed

    Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus Medical Center, Rotterdam, the Netherlands

16. Erik Scholten

    St. Antonius Ziekenhuis

    Affiliation as printed

    Department of Intensive Care, Sint Antonius Hospital, Nieuwegein, the Netherlands

17. Albertus Beishuizen

    Medisch Spectrum Twente

    Affiliation as printed

    Department of Intensive Care, Medisch Spectrum Twente, Enschede, the Netherlands

18. Chris P. H. Lexis

    Maastricht University Medical Centre · Maastricht University

    Affiliation as printed

    Department of Intensive Care and Cardiology, Maastricht UMC, Maastricht, the Netherlands

19. Harlinde Peperstraete

    Ghent University Hospital

    Affiliation as printed

    Department of Intensive Care, Ghent University Hospital, Ghent, Belgium

20. Simon Schiettekatte

    Ziekenhuis Oost-Limburg

    Affiliation as printed

    Department of Cardiac Surgery, Ziekenhuis Oost-Limburg Genk, Genk, Belgium

21. Roberto Lorusso

    Maastricht University Medical Centre · Maastricht University

    Affiliation as printed

    Department of Cardiothoracic Surgery and Cardiovascular Research Center, Maastricht UMC, Maastricht, the Netherlands

22. Diederik A M P J Gommers

    Erasmus MC

    Affiliation as printed

    Department of Intensive Care, Erasmus Medical Center, Rotterdam, the Netherlands

23. Dick Tibboel

    Erasmus MC

    Affiliation as printed

    Department of Intensive Care, Erasmus Medical Center, Rotterdam, the Netherlands

24. Rudolf A. de Boer

    Erasmus MC

    Affiliation as printed

    Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus Medical Center, Rotterdam, the Netherlands

25. Nicolas M. Van Mieghem

    Erasmus MC

    Affiliation as printed

    Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus Medical Center, Rotterdam, the Netherlands

26. Christiaan Lucas Meuwese

    Erasmus MC

    Affiliation as printed

    Department of Intensive Care, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Cardiology, Thorax Center, Cardiovascular Institute, Erasmus Medical Center, Rotterdam, the Netherlands. Electronic address: c.meuwese@erasmusmc.nl