A prospective evaluation of edoxaban compared to warfarin in subjects undergoing cardioversion of atrial fibrillation: the EdoxabaN vs. warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF STUDY)

We designed a prospective, randomized, open-label, blinded endpoint evaluation(PROBE) parallel group Phase 3b clinical trial comparing edoxaban (a new oral factor Xa inhibitor) with enoxaparin/warfarin followed by warfarin alone in subjects undergoing planned electrical cardioversion of non-valvular AF. The primary efficacy endpoint is the composite endpoints of stroke, systemic embolic event (SEE), myocardial infarction (MI) and cardiovascular (CV) mortality, from randomization until the end of follow-up (Day 56 post cardioversion). The primary safety endpoint is the composite of major and clinically-relevant non-major (CRNM) bleeding, from the first administration of study drug to end of treatment (Day 28 post cardioversion) + 3 days. The primary efficacy analysis will be conducted on the intention-to-treat population whereas the primary safety analysis – on the safety population (refer to definitions in the main text).
The study includes stratification on the following levels: (i) approach to cardioversion (transoesophagel echocardiography (TEE) or non-TEE) as determined by the Investigator; (ii) subject’s experience in taking anticoagulants at the time of randomization (anticoagulant-experienced or anticoagulant-naïve); and (iii) assigned edoxaban dose (full 60 mg QD or reduced 30 mg dose QD). A subject with one or more factors (CrCl ≥ 15mL/min and ≤ 50 mL/min, low body weight [≤60 kg], and concomitant use of p-pg inhibitors (excluding amiodarone) will receive a reduced dose (30 mg) of edoxaban if the subject is randomized to the edoxaban group.
ENSURE-AF will be the largest prospective randomised trial of anticoagulation for cardioversion, also involving a NOAC, edoxaban.