Optimising trial design for cardiogenic shock: insights from the sixth Critical Care Clinical Trialists Workshop.

Naoki Sato, Rhonda E Monroe, Shashank S Sinha, Connor O'Brien, Alexandre Mebazaa, Nadia Aissaoui, Alain Combes, Antoine Kimmoun, Rebecca Mathew, Jacob E Møller, Florian A Wenzl, Susanna Price, Uwe Zeymer, Sabri Soussi, Janine Pöss, Vanessa Blumer, Alessandro Sionis

Journal: The Lancet. Respiratory medicine 2025;13(9):833-842

PMID: 40339587

Full Text on Elsevier Science View on PubMed

Abstract

Despite substantial advancements in the management of cardiogenic shock, mortality rates remain greater than 40%. Trials have shown that increasing survival rates in cardiogenic shock is challenging. Even the most successful trials show 5-15% reductions in mortality, and gains have been restricted to acute myocardial infarction cardiogenic shock, representing approximately 5% of the population with cardiogenic shock. Trials studying pharmacological strategies in all populations with cardiogenic shock have been consistently neutral or negative. The reasons are complex and include heterogeneity in cardiogenic shock phenotypes, timing of patient inclusion, high prevalence of multiorgan failure and cardiac arrest, and unrealistic estimated treatment effects that restrict sample size with sometimes inadequate funding leading to underpowered trials. In June, 2024, international experts from the fields of cardiology, anaesthesiology, critical care medicine, biostatistics, government regulation of trials, and patient advocacy convened at the sixth Critical Care Clinical Trialists Workshop to reflect on how to improve the design of future randomised clinical trials in cardiogenic shock. This Position Paper summarises the results of discussions regarding what an optimal randomised controlled trial on cardiogenic shock should entail in terms of population selection, primary objectives, statistical analysis, and incorporation of the patient's perspective.

Address: Lorraine University, Nancy Teaching Hospital, Intensive care unit, INSERM U1116, Nancy, France.; Division of Cardiology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.; Inova Schar Heart and Vascular, Inova Fairfax Medical Campus, Falls Church, VA, USA.; Center for Molecular Cardiology, University of Zürich, Schlieren, Switzerland; National Disease Registration and Analysis Service, NHS, London, UK; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK; Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden.; Heart Center Leipzig at University of Leipzig, Leipzig, Germany.; Institut für Herzinfarktforschung Ludwigshafen, Ludwigshafen, Germany; Department of Cardiology and Angiology, University Heart Center Freiburg, University of Freiburg, Bad Krozingen, Germany.; Department of Cardiology, Odense University Hospital, Odense, Denmark; Clinical Institute University of Southern Denmark, Odense, Denmark.; Service de Cardiologie, Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France.; Sorbonne Université, INSERM, Institute of Cardiometabolism and Nutrition, and Service de Médecine Intensive-Réanimation, Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France.; Department of Cardiovascular Medicine, Kawaguchi Cardiovascular and Respiratory Hospital, Kawaguchi, Japan.; Unidad de Cuidados Intensivos Cardiológicos, Servicio de Cardiología, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Instituto de Investigación Biomédica Sant Pau (IIB Sant Pau), Barcelona, Spain; Universidad Autónoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Cardiovasculares, Madrid, Spain.; Department of Anesthesia and Pain Management, University Health Network, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada; Shock and Acute Conditions Outcomes Platform Consortium, Toronto, ON, Canada; Inserm UMR-S 942 MASCOT, Cardiovascular Markers in Stress Conditions, University of Paris Cité, Paris, France.; National Heart and Lung Institute, Imperial College, London, UK; Department of Critical Care and Department of Cardiology, Royal Brompton and Harefield Hospitals, London, UK.; Better Outcomes Optimal Scientific Therapies, Charlotte, NC, USA.; Department of Critical Care, University of Ottawa, Ottawa, ON, Canada; CAPITAL Research Group, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada.; Inserm UMR-S 942 MASCOT, Cardiovascular Markers in Stress Conditions, University of Paris Cité, Paris, France; Université Paris Cité, Paris, France; Department of Anesthesiology and Critical Care and Burn Unit, Saint-Louis and Lariboisière Hospitals, AP-HP Nord, Paris, France. Electronic address: [email protected].

DOI: 10.1016/S2213-2600(25)00084-0

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MeSH Terms: Humans, Shock, Cardiogenic, Critical Care, Randomized Controlled Trials as Topic, Research Design