Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Edoxaban vs. Warfarin in Subjects Undergoing Cardioversion of Atrial Fibrillation (ENSURE-AF)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Daiichi Sankyo Inc.
Information provided by (Responsible Party):
Daiichi Sankyo Inc. Identifier:
First received: February 20, 2014
Last updated: December 1, 2014
Last verified: March 2014

The purpose of this study is to compare edoxaban (investigational drug) with warfarin and enoxaparin, to see if it is safe and effective in preventing stroke and other blood clot complications in subjects with atrial fibrillation whose doctors plan to treat them with an electrical cardioversion. It is expected that 284 sites will recruit 2200 subjects from North America, EU, Russia, Ukraine and Israel. Participants will be randomly allocated to receive either treatment with edoxaban, or treatment with warfarin, plus enoxaparin if required. Participants will have an equal chance of receiving either treatment. Participants will be in the study for a maximum of 82 days. Study procedures will include physical examinations, vital signs (pulse and sitting blood pressure), ECG (electrocardiogram), finger prick blood clotting tests, blood samples, urine samples and completion of Quality of Life questionnaires.

The study is expected to show that edoxaban will provide comparable incidence rates for efficacy to warfarin plus enoxaparin, the current standard treatment, and will be at least as safe as warfarin for the incidence rate for bleeding

Condition Intervention Phase
Atrial Fibrillation
Drug: edoxaban
Drug: Enoxaparin
Drug: Warfarin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective, Randomized, Open-Label Blinded Endpont Evaluation (PROBE) Parallel Group Study Comparing Edoxaban (DU-176b) With Enoxaparin/Warfarin Followed by Warfarin Alone in Subjects Undergoing Planned Electrical Cardioversion of Nonvalvular Atrial Fibrillation

Resource links provided by NLM:

Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • incidence of composite CV endpoints [ Time Frame: 58 days ] [ Designated as safety issue: No ]
    Compare the incidences of the composite endpoints of stroke, systemic embolic event (SEE), myocardial infarction (MI) and cardiovascular (CV) mortality between the edoxaban group and the enoxaparin/warfarin group from randomization to end of follow up (FU) 58 days post cardioversion.

  • incidence of major and CRNM bleeding [ Time Frame: 61 days ] [ Designated as safety issue: Yes ]
    Compare the incidence of the composite endpoints of major and clinically-relevant non-major (CRNM) bleeding between the edoxaban group and the enoxaparin/warfarin group from randomization to end of treatment (58 days post cardioversion) + 3 days

Secondary Outcome Measures:
  • incidence of composite CV endpoints and major bleeding [ Time Frame: 58 days ] [ Designated as safety issue: Yes ]
    Compare the incidences of the composite endpoints of stroke, systemic embolic event (SEE), myocardial infarction (MI), cardiovascular (CV) mortality and major bleedings between the edoxaban group and the enoxaparin/warfarin group from randomization to end of FU (58 days post cardioversion).

Estimated Enrollment: 2200
Study Start Date: March 2014
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: edoxaban treatment
Factor Xa inhibitor anticoagulant, oral, edoxaban tablet, 60 or 30 mg QD,28-49 days dosing
Drug: edoxaban
Factor Xa inhibitor anticoagulant, oral, edoxaban tablet, 60 or 30 mg once-daily (QD), 28-49 days dosing
Active Comparator: enoxaparin / warfarin
Vitamin K antagonist, sq/oral, 100mg/kg or 1 or 2.5 mg tablet QD, 28-49 days
Drug: Enoxaparin
Vitamin K antagonist, sq, 100mg/kg, 28-49 days
Drug: Warfarin
Vitamin K antagonist, oral, 1 or 2.5 mg tablet QD, 28-49 days


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Signed informed consent
  • Male or female older than minimum legal adult age (country specific)
  • Ongoing AF lasting at least 48 hrs but <= 12 months

Exclusion Criteria:

  • .AF that is transient or reversible
  • No other rhythm issues other than AF
  • Mitral stenosis or rheumatic disease, unresected atrial myxoma or mechanical heart valve
  • Left atrial appendage closure or thrombus
  • MI, stroke, ACS, PCI within 30 days
  • High risk of bleeding within 10 days or randomization
  • Dual antiplatelet therapy
  • List of prohibited concomitant medication
  • Active liver disease
  • Renal failure, CrCl < 15 ml/min
  • Hemoglobin < 10g/dl or platelet count < 100000 cells/microliter
  • Taking other investigational drugs
  • Women of childbearing potential with proper contraceptives measures
  • Active cancer requiring chemotherapy/radiation/surgery
  • Investigator discretion based on examination
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02072434

Contact: Cain Price 44-162854-8000
Contact: Yuk-Fung Keane 44-162854-8000

United States, Arizona
Phoenix, Arizona, United States
United States, California
San Diego, California, United States
United States, Colorado
Greeley, Colorado, United States
United States, Connecticut
Stamford, Connecticut, United States
United States, Delaware
Newark, Delaware, United States
United States, Florida
Clearwater, Florida, United States
Daytona Beach, Florida, United States
United States, Pennsylvania
Camp Hill, Pennsylvania, United States
Ephrata, Pennsylvania, United States
United States, South Dakota
Rapid City, South Dakota, United States
United States, Texas
Active, not recruiting
Dallas, Texas, United States
Pees, Hungary
Sponsors and Collaborators
Daiichi Sankyo Inc.
Principal Investigator: Andreas Goette, MD Kardiologie und Internistische Intensivmedizin
  More Information

Responsible Party: Daiichi Sankyo Inc. Identifier: NCT02072434     History of Changes
Other Study ID Numbers: DU176b-F-E308
Study First Received: February 20, 2014
Last Updated: December 1, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Daiichi Sankyo Inc.:
Atrial fibrillation
electrical cardioversion

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses processed this record on February 27, 2015