A PHASE 3, RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, PARALLEL GROUP, MULTI-CENTER, MULTI-NATIONAL STUDY FOR EVALUATION OF EFFICACY AND SAFETY OF DU-176B VERSUS WARFARIN IN SUBJECTS WITH ATRIAL FIBRILLATION – Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation (ENGAGE-AF) - ENGAGE AF TIMI-48

Conditions: Reduction of Stroke and/or systemic embolic event (SEE) in subjects with atrial fibrillation (AF).
MedDRA version: 9.1Level: LLTClassification code 10003658Term: Atrial fibrillation

Registration Number: EUCTR2008-004522-16-PT

Lead Sponsor: Daiichi Sankyo Pharma Development

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 20500

Inclusion Criteria

1. Male or female subjects with age = 21 years;
2. Able to provide written informed consent;
3. History of AF documented by any electrical tracing (routine 12-lead electrocardiographic reading [ECG], Holter monitor [continuous ECG recording], rhythm strip, intracardiac electrogram, or pacemaker [PM] or implantable cardiac defibrillator [ICD] interrogation) within the prior 12 months and for which anticoagulation therapy is indicated and planned for the duration of the study; subjects with AF includes subjects with paroxysmal, persistent, or permanent AF and subjects with or without previous VKA (including warfarin) experience (it is anticipated that approximately 40% of subjects will be VKA-naive);
4. Subjects must have a CHADS2 index score of = 2. The CHADS2 scoring is performed by assigning 1 point each for a history of congestive heart failure, hypertension, age = 75 years, or diabetes mellitus; and by assigning 2 points for history of stroke or TIA.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects who meet any of the criteria below will be disqualified from entering the study.
1. Transient AF secondary to other reversible disorders (e.g., thyrotoxicosis, cardiac or thoracic surgery, pneumonia, severe anemia);
2. Subjects with moderate or severe mitral stenosis due to rheumatic heart disease, unresected atrial myxoma, or a mechanical heart valve (subjects with bioprosthetic heart valves and/or valve repair can be included);
• However, subjects with AF and valvular heart diseases such as mitral valve prolapse, mitral valve regurgitation, and aortic valve disease are allowed in the study as long as the valvular heart disease is not due to rheumatic heart disease;
3. Subjects with a history of left atrial appendage exclusion (either by surgery or by a procedure);
4. Subjects with intracardial mass or left ventricular thrombus;
5. Subjects for whom discontinuation of chronic anticoagulation therapy will be considered if a planned pharmacologic, electrical or surgical therapy were to be successful in converting the subject to normal sinus rhythm (NSR) and maintaining that rhythm;
6. Subjects with any contraindication for anticoagulant agents;
7. Subjects with conditions associated with high risk of bleeding such as past history of spontaneous intracranial, intraocular, spinal, retroperitoneal, or intra-articular bleeding; overt gastrointestinal (GI) bleeding or active ulcer within the previous year; recent severe trauma, major surgery, or deep organ biopsy within the previous 10 days; active infective endocarditis; uncontrolled hypertension (blood pressure [BP] above 170/100 mmHg); or hemorrhagic disorder including known or suspected hereditary or acquired bleeding or coagulation disorder;
8. Subjects receiving dual antiplatelet therapy (e.g. aspirin plus thienopryridine such as ticlopidine or clopidogrel) or anticipated to receive such therapy unless all but one of the antiplatelet medications can be safely stopped prior to randomization and while receiving study drug;
9. Subjects receiving chronic cyclosporine therapy;
10. Subjects receiving prohibited concomitant medications (fibrinolytics, non-study anticoagulants other than those used as a bridge to/from study drug, chronic non-aspirin NSAID use for = 4 days/week, and potent P-gp inhibitors as defined for this study;
11. Subjects with acute MI, stroke, acute coronary syndrome (ACS), or percutaneous coronary intervention (PCI) within the previous 30 days;
12. Subjects with active liver disease or persistent (confirmed by repeat assessments at least a week apart) elevation of liver enzymes/bilirubin:
• ALT or AST = 2 times the ULN;
• TBL =1.5 times the ULN (however, subjects whose elevated TBL is due to known Gilbert's syndrome may be included in the study);
13. Subjects with severe renal insufficiency (calculated CrCL <30 mL/min);
14. History of testing positive Hepatitis B antigen or Hepatitis C antibody before randomization;
15. Any other clinically relevant laboratory abnormality as judged by the Investigator;
16. Subjects with a known history of testing positive for human immunodeficiency virus (HIV);
17. Subjects with hemoglobin < 10 g/dL or platelet count < 100,000 cells/µL or white blood cell count (WBC) < 3000 cells/µL;
18. Subjects with pre-planned invasive procedures (other than routine endoscopy) or surgeries in which bleeding is anticipated during the study period;
19. Subjects who received any investigational drug or device within 30 days prior to randomiza