Dronedarone vs class Ic agents for early AF: Protocol for the DRIVE-AF randomized clinical trial.

Background: Early rhythm control is crucial in atrial fibrillation (AF), yet clinical equipoise remains regarding the optimal initial antiarrhythmic drug (AAD). Although class Ic agents are widely used, their safety profile often necessitates complex coadministration with rate-control drugs, potentially limiting adherence. Dronedarone offers distinct safety advantages, but direct randomized comparisons with class Ic agents in early AF are lacking. Objective: This study aimed to test the hypothesis that dronedarone is noninferior to class Ic AADs regarding efficacy (AF recurrence) and superior regarding safety (drug discontinuation owing to adverse events). Methods: The Dronedarone Rhythm Intervention for Early Atrial Fibrillation trial is a prospective, multicenter, randomized, open-label trial to be conducted at 14 academic centers in Korea. The study will enroll 1898 patients diagnosed as having AF within 12 months who require AAD therapy. Participants will be randomized (1:1) to receive either dronedarone (400 mg twice daily) or standard-of-care class Ic agents (flecainide or propafenone) for 12 months. Results: The dual primary endpoints are AF recurrence at 12 months (noninferiority) and drug discontinuation owing to adverse events (superiority). Secondary outcomes include AF-specific quality of life, medication adherence (proportion of days covered), and major adverse cardiovascular events. Analyses will be performed on both intention-to-treat and per-protocol bases. Conclusion: The Dronedarone Rhythm Intervention for Early Atrial Fibrillation trial is the first large-scale, randomized trial directly comparing the "safety-first" strategy of dronedarone with the traditional class Ic strategy. By establishing comparative efficacy and safety, this study aims to refine international standards for pharmacologic rhythm control in early AF. Trial registration: ClinicalTrials.gov identifier: NCT07270848.