Phase 2 Study of the Safety, Tolerability and Pilot Efficacy of Oral Factor Xa Inhibitor Betrixaban Compared to Warfarin
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Intervention: betrixaban; Warfarin
Intervention description: orally, once daily for at least 3 months; Warfarin will be prescribed by the investigator according to the standard of care.
Intervention MeSH terms: Warfarin; Acenocoumarol; Betrixaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 508.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Atrial Fibrillation; Betrixaban; Factor Xa inhibitor; Warfarin

Summary:

      Prevention of stroke in patients with atrial fibrillation (AF). Hypothesis: In patients with
      non-valvular AF, orally administered betrixaban will provide similar or better efficacy and
      safety than warfarin and it will offer the advantage of not requiring dose adjustments due to
      international normalized ratios (INRs) outside the target range of 2.0 to 3.0 and a more
      consistent level of anticoagulation over time.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, age ≥18 years.

          -  If the patient is a woman, she must be without reproductive potential (i.e.,
             postmenopausal for ≥2 years or after hysterectomy).

          -  AF at the time of enrollment (randomization) or documented within the last year by
             Holter, ECG, rhythm strip, pacemaker or other intracardiac recording, resulting in an
             indication for anticoagulation with warfarin, acenocumerol, phenprocoumon, or other
             Vitamin K antagonist in the opinion of the treating physician.

          -  One or more of the following risk factor(s) for stroke:

               1. Age 75 years or older.

               2. Prior stroke, TIA or systemic (i.e., central nervous system) embolus at least 30
                  days remote from the time of screening.

               3. Symptomatic congestive heart failure within 3 months echocardiography,
                  radionuclide study or contrast angiography.

               4. Hypertension requiring pharmacological treatment.

               5. Diabetes.

               6. Age of 55 years or older and previous coronary artery disease or known peripheral
                  artery disease.

        Exclusion Criteria:

          -  Body weight less than 40 kg (88 lbs).

          -  Need for either hemodialysis or peritoneal dialysis (or likely to require it within
             one year).

          -  AF due to reversible causes (e.g., thyrotoxicosis, pericarditis, cardiac surgery,
             pulmonary embolism).

          -  Mechanical prosthetic valve (bioprosthetic valve is allowed) or valvular disease
             likely to be operated on within one year.

          -  History (including family history) or symptoms of a congenital or acquired bleeding
             disorder or vascular malformation; or a history of intracranial, retroperitoneal, or
             intraocular bleeding within the last 6 months; or is felt to be at high risk for
             bleeding for other reasons including from significant liver disease. This also
             includes gastrointestinal bleeding within 90 days before randomization or
             endoscopically verified ulcer disease within 30 days of screening.

          -  Conditions other than AF that require chronic anticoagulation (e.g. prosthetic
             mechanical heart valve).

          -  Persistent, uncontrolled hypertension (SBP >160 mm Hg on repeated measurements).

          -  Active infective endocarditis.

          -  Scheduled major surgery.

          -  Planned pulmonary vein ablation or surgical procedure for cure of AF or flutter.

          -  Recent ischemic stroke, systemic embolic event or acute coronary syndrome within 30
             days.

          -  Severe co-morbid condition with life expectancy of ≤1 year.

          -  Previous known history of genetic coagulopathy (e.g., Factor V Leiden, Protein C
             Deficiency, Protein S Deficiency, Antiphospholipid Syndrome, etc.).

          -  Evidence at Screening of:

               1. Platelet count <100,000/mm3.

               2. Serum alanine aminotransferase (ALT) or aspirate aminotransferase (AST) >2 times
                  upper limit of normal (ULN).

               3. A history (including family history) of "Long QT Syndrome".

          -  Aspirin >162 mg daily.

          -  Use of verapamil (pending the availability of a drug interaction study with
             betrixaban).

          -  Active alcohol or drug abuse, or psychosocial reasons that make study participation
             impractical.

          -  Use of an investigational drug or device within the past 30 days.

          -  Inability to comply with INR monitoring or other protocol-related activities.

          -  Unable to give written informed consent.