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

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.