In This SectionTexas Health Research & Education Institute
Disease or Condition
Heart / Atrial Fibrillation
Comparison to warfarin in patients with Atrial Fibrillation (Heart / Atrial Fibrillation)
Global Study to assess the safety and effectiveness of DU-176b vs standard practice of dosing with warfarin in patients with atrial fibrillation.
Male or female subjects with age ≥ 21 years.
Able to provide written informed consent.
Must be able to read, write and speak English.
History of AF documented by any electrical tracing (routine 12-lead electrocardiogram [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).
Subjects must have a CHADS2 index score ≥ 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.
Transient AF secondary to other reversible disorders (e.g., thyrotoxicosis, cardiac or thoracic surgery, pneumonia, severe anemia).
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.
Subjects with a history of left atrial appendage exclusion (either by surgery or by a procedure).
Subjects with intracardial mass or left ventricular thrombus.
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.
Subjects with any contraindication for anticoagulant agents.
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.
Subjects receiving dual antiplatelet therapy (e.g., aspirin plus thienopyridine 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.
Subjects receiving chronic cyclosporine therapy.
Subjects receiving prohibited concomitant medications (fibrinolytics, non-study anticoagulants other than those used as a bridge to/from study drug, chronic nonaspirin NSAID use for ?4 days/week, and potent P-gp inhibitors as defined for this study.
Subjects with acute MI, stroke, acute coronary syndrome (ACS), or percutaneous coronary intervention (PCI) within the previous 30 days.
Subjects with active liver disease or persistent (confirmed by repeat assessments at least a week apart) elevation of liver enzymes/bilirubin:
a. ALT or AST ≥ 2 times the ULN.
b. TBL 1.5 times the ULN (however, subjects whose elevated TBL is due to known Gilbert’s syndrome may be included in the study).
Subjects with severe renal insufficiency (calculated CrCL <30 mL/min).
History of testing positive for Hepatitis B antigen or Hepatitis C antibody before randomization.
Any other clinically relevant laboratory abnormality as judged by the Investigator.
Subjects with a known history of testing positive for human immunodeficiency virus (HIV).
Subjects with Hgb < 10 g/dL or platelet count < 100,000 cells/?L or white blood cell count (WBC) < 3000 cells/L.
Subjects with pre-planned invasive procedures (other than routine endoscopy) or surgeries in which bleeding is anticipated during the study period.
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.
Subjects previously randomized in a DU-176b study.
Females of childbearing potential including the following:
a. Females with a history of tubal ligation.
b. Females less than 2 years postmenopausal.
Subjects with the following diagnoses or situations:
a. Active malignancy (diagnosed within 5 years) except for adequately treated non-melanoma skin cancer or other non-invasive or in-situ neoplasm (e.g., cervical cancer in situ).
b. Treatment with anti-cancer therapy (drugs, radiation, and/or surgery) within the last 5 years.
c. Significant active concurrent medical illness or infection.
d. Life expectancy < 12 months.
Subjects who are unlikely to comply with the protocol (e.g., uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study).
Subjects with a known drug or alcohol dependence within the past 12 months as judged by the Investigator.
Subjects with any condition that, in the opinion of the Investigator, would place the subject at increased risk of harm if he/she participated in the study.