Evaluating Multiple Treatments and Strategies for Sepsis in Adaptive Platform (EURASSIA) trial in Japan: a core protocol.

INTRODUCTION: Sepsis is a life-threatening infectious disease with increasing prevalence. Although several studies have reported high-quality evidence, therapeutic strategies still require further development to reduce the high mortality associated with sepsis. However, small effects of newly proposed treatments due to heterogeneity in sepsis hinder the feasibility of randomised controlled trials, a standard resource-demanding approach to validate benefits of therapy. This trial aims to rapidly evaluate various treatments and strategies for sepsis through an adaptive platform trial (APT) established as a semipermanent study platform.

METHODS AND ANALYSIS: The Evaluating Multiple Treatments and Strategies for Sepsis in Adaptive Platform (EURASSIA) trial is an APT, incorporating 11 tertiary care centres in Japan. This trial was initiated in 2024 with two domains, where two different interventions will be separately and simultaneously investigated in a randomised controlled design. Domains will be added and removed during the conduct of this semipermanent trial. The EURASSIA trial will include adult patients with sepsis who require intensive care whereas those with withheld/withdrawn care at sepsis diagnosis will be excluded. Subsequently, eligibility will be assessed for each domain, and participants will be randomly assigned to either intervention in each domain (eg, intravenous low-dose landiolol or no medication for mild tachycardia in the haemodynamic management domain and chlorhexidine-containing or usual dressing for a catheter insertion site in the infection control domain). The primary outcome is 90-day survival after intensive care initiation for sepsis; however, additional outcomes will be defined at the domain admission. The outcome will be analysed following a statistical analysis plan that will be predefined in each domain. Although reweighted response-adaptive randomisation will not be adopted, intervention-by-subtype interactions will be assessed across the domains at interim and final analyses to modify the sample size and add a stratification factor for random allocation as needed.

ETHICS AND DISSEMINATION: The Certified Review Board of Keio at the principal institution approved this study (approval number: N20240002). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations.

TRIAL REGISTRATION NUMBER: jRCT1031240424.