Rationale and methods of the Advanced R²Eperfusion STrategies for Refractory Cardiac Arrest (ARREST) trial

Background: Venoarterial extracorporeal membrane oxygenation has emerged as a prominent therapy for patients with refractory cardiac arrest. However, the optimal time of initiation remains unknown. Aim: The aim was to assess the rate of survival to hospital discharge in adult patients with refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest treated with 1 of 2 local standards of care: (1) early venoarterial extracorporeal membrane oxygenation–facilitated resuscitation for circulatory support and percutaneous coronary intervention, when needed, or (2) standard advanced cardiac life support resuscitation. Design: Phase II, single-center, partially blinded, prospective, intention-to-treat, safety and efficacy clinical trial. Population: Adults (aged 18–75), initial out-of-hospital cardiac arrest rhythm of ventricular fibrillation/pulseless ventricular tachycardia, no ROSC following 3 shocks, body morphology to accommodate a Lund University Cardiac Arrest System automated cardiopulmonary resuscitation device, and transfer time of <30 minutes. Setting: Hospital-based. Outcomes: Primary: survival to hospital discharge. Secondary: safety, survival, and functional assessment at hospital discharge and 3 and 6 months, and cost. Sample size: Assuming success rates of 12% versus 37% in the 2 arms and 90% power, a type 1 error rate of .05, and a 15% rate of withdrawal prior to hospital discharge, the required sample size is N = 174 evaluated patients. Conclusions: The ARREST trial will generate safety/effectiveness data and comparative costs associated with extracorporeal cardiopulmonary resuscitation, informing broader implementation and a definitive Phase III clinical trial.