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

Phase 1

Conditions: Prevention 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-SK

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 a 12-lead electrocardiographic reading and/or continuous electrocardiogram (ECG) (e.g., Holter monitoring) consistent with AF (notation of AF as the abnormal rhythm on the local ECG report with evidence of irregularly irregular rhythm and an absence of P-waves on the ECG for diagnosis of AF) within the prior 12 months and for which anticoagulation therapy is indicated and planned for the duration of the study, including 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.A moderate to high risk of stroke, as defined by CHADS2 index score of at least 2, is required to be eligible for the study. 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, unresected atrial myxoma, or a mechanical heart valve (subjects with bioprosthetic heart valves and/or valve repair can be included);
3.Subjects for whom the AF management plan is rhythm control with subsequent discontinuation of oral anticoagulation if sinus rhythm is restored or maintained, including subjects in whom successful electrical or surgical ablation has been performed or is planned during the course of the study;
4.Subjects with any contraindication for anticoagulant agents;
5.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;
6.Subjects receiving thienopyridines (such as ticlopidine or clopidogrel) or other non-aspirin antiplatelet agents that cannot be stopped at randomization, or who are anticipated to receive non-aspirin antiplatelet agents as chronic therapy during the study;
7.Subjects receiving chronic cyclosporine for organ transplant, rheumatoid arthristis, or psoriasis;
8.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 or for a chronic condition, potent P-gp inhibitors [ritonavir, cyclosporine, ketoconazole, itraconazole, erythromycin, clarithromycin];
9.Subjects with acute MI, stroke, acute coronary syndrome (ACS), or percutaneous coronary intervention (PCI) within the previous 30 days;
10.Subjects with active liver disease or persistent (confirmed by repeat assessment within a week) elevation of liver enzymes/bilirubin:
•ALT or AST = 2 times the ULN,
•TBL =1.5 times the ULN,
•ALP =2 times the ULN;
11.Subjects with severe renal insufficiency (calculated CrCL <30 mL/min);
12.History of positive Hepatitis B antigen or Hepatitis C antibody;
13.Any other clinically relevant laboratory abnormality as judged by the Investigator;
14.Subjects receiving antiretroviral therapy for human immunodeficiency virus (HIV) infection or likely to receive such therapy during the study;
15.Subjects with hemoglobin < 10 g/dL or platelet count < 100,000 cells/µL or white blood cell count (WBC) < 3000 cells/µL;
16.Subjects with pre-planned invasive procedures (other than routine endoscopy) or surgeries in which bleeding is anticipated during the study period;
17.Subjects who received any investigational drug or device within 30 days prior to randomization, or plan to receive such investigational therapy during the study period;
18.Subjects previously randomized in a DU-176b study;
19.Females of childbearing potential including including the following:
•Females with a history of tubal ligation;
•Females less than 2 years postmenopausal;
20.Subjects with the following diagnoses or situations:
•Activ