Strategies for Defibrillation during Out-of-Hospital Cardiac Arrest – Protocol for a Randomised Clinical Trial

Background There is a lack of evidence regarding which defibrillation strategy is the most effective during resuscitation. Anterior-posterior pad placement and double sequential defibrillation have been proposed as alternatives to standard anterior-lateral defibrillation for patients with refractory shockable rhythms, but evidence remains limited. Objective This trial will investigate whether there is a difference in 30-day survival when using anterior-posterior and double sequential defibrillation as compared to standard anterior-lateral defibrillation in adults with out-of-hospital cardiac arrest and a shockable rhythm. Methods This trial is an investigator-initiated, individually randomised, 3-group, clinical trial enrolling adult patients with out-of-hospital cardiac arrest with at least one emergency medical services defibrillation attempt and if the last known rhythm is shockable and two manual defibrillators are available. Participants are randomised 1:1:1 to anterior-lateral defibrillation, anterior-posterior defibrillation, or double sequential defibrillation The trial is planned to be conducted in Denmark, Finland, Belgium, and Ireland. The primary outcome is 30-day survival, with key secondary outcomes of 90-day survival and neurological status at 30 and 90-days assessed using the modified Rankin Scale. Additional outcomes include return of spontaneous circulation, hospital disposition, health-related quality of life, and longer-term survival and neurological outcomes. The planned sample size is 909 participants. Enrollment began in March 2025. 320 patients have been enrolled by September 2026. The trial is registered at ClinicalTrials.gov (identifier: NCT06781892).