Background: Despite significant advances in resuscitation efforts, there are some patients who remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Double sequential external defibrillation (DSED) and vector change defibrillation (VC) have been proposed as alternate therapeutic strategies for OHCA patients in shock-refractory VF. Objective: To determine the feasibility, safety and sample size required for a larger, multicentered, 3-arm, cluster randomized controlled trial (RCT) with 2 crossovers comparing DSED or VC to standard defibrillation (control group) for OHCA patients presenting in shock-refractory VF. Methods: We conducted a pilot cluster randomized controlled trial with crossover including all consecutive treated adult OHCA patients who presented in VF and received a minimum of three successive shocks. In addition to standard cardiac arrest care, each EMS agency was randomly assigned to provide standard defibrillation (control), DSED, or VC, followed by crossover to an alternate defibrillation strategy after 6 months. Results: Prior to the launch of the trial, 2,500 paramedics received in-person training in the techniques of DSED and VC defibrillation using a combination of didactic, video and simulated scenarios. Between March 2018 and June 2019, 113 patients were enrolled in 4 Canadian EMS agencies, with zero missed cases. Monthly enrollment varied from 1 to 6 cases per agency. With respect to feasibility, 96% of cases were compliant with the study protocol, and only five (4.4%) cases received a defibrillation strategy that differed from the allocation schedule. There were no reported cases of defibrillator malfunction, no concerns expressed by paramedics, patients, families, or ED staff about the trial, and no reported cases of skin burns or difficulty with pad placement. Conclusions: Findings from our pilot implementation trial suggest the DOSE VF protocol is feasible and safe. The results of this internal pilot trial will allow us to calculate a sample size for a definitive multicenter cluster RCT with crossovers to determine if these alternate defibrillation strategies for OHCA shock refractory VF will impact patient-centered, clinical outcomes.