title: 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.
abstract: We designed a prospective, randomized, open-label, blinded end point evaluation 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 atrial fibrillation. The primary efficacy end point is the composite end points of stroke, systemic embolic event, myocardial infarction, and cardiovascular (CV) mortality, from randomization until the end of follow-up (day 56 post cardioversion). The primary safety end point is the composite of major and clinically-relevant non-major 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. The study includes stratification on the following levels: (i) approach to cardioversion (transoesophagel echocardiography or non-transoesophagel echocardiography) 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 ≥15 mL/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 Non-VKA Oral Anticoagulant-edoxaban.
authors.affiliation: University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom; Aalborg University, Denmark. Electronic address: g.y.h.lip@bham.ac.uk.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.affiliation: University Hospital La Paz - IdiPaz, Madrid, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Merino
authors.affiliation: Jefferson Medical College, Cardiovascular Research Foundation, New York, NY.
authors.forename: Michael
authors.initials: M
authors.lastname: Ezekowitz
authors.affiliation: VCU School of Medicine, Richmond, VA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Ellenbogen
authors.affiliation: Daiichi Sankyo Development Ltd., Gerrards Cross, UK.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Zamoryakhin
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: Hans
authors.initials: H
authors.lastname: Lanz
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: James
authors.initials: J
authors.lastname: Jin
authors.affiliation: Covance Inc., Maidenhead, UK.
authors.forename: Naab
authors.initials: N
authors.lastname: Al-Saadi
authors.affiliation: Daiichi Sankyo Pharma Development, Edison, NJ.
authors.forename: Michele
authors.initials: M
authors.lastname: Mercuri
authors.affiliation: Department of Cardiology and Intensive Care Medicine, St. Vincenz-Hospital, Paderborn and Working Group of Molecular Electrophysiology, University Hospital Magdeburg, Magdeburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Goette
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications / Q000188:drug therapy / Q000628:therapy*; D002318:Cardiovascular Diseases / Q000401:mortality; D004554:Electric Countershock; D065427:Factor Xa Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011446:Prospective Studies; D011725:Pyridines / Q000627:therapeutic use*; D012107:Research Design; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D013844:Thiazoles / Q000627:therapeutic use*; D013923:Thromboembolism / Q000209:etiology / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; D014859:Warfarin; C552171:edoxaban