Official Title: “Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke or Systemic Embolism in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment: A Randomized Double Blind Trial”

The purpose of this clinical research study is to learn if apixaban is more effective than Acetylsalicylic Acid (ASA) in preventing strokes and systemic embolisms associated with subjects who have atrial fibrillation. The safety of this treatment will also be studied.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Investigator), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: April 2010

Intervention(s) in this Clinical Trial

• Drug: Apixaban
  • Tablets, Oral, 5 mg (2.5 mg in selected patients), BID, Up to 36 months/End of Study
• Drug: Acetylsalicylic Acid (ASA)
  • Tablets, Oral, 81 - 324 mg, QD, Up to 36 months/End of Study

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: I
• Placebo Comparator: II

Primary Measures

• To determine if apixaban 5 mg BID (2.5 mg BID in selected patients) is superior to ASA (81 to 324 mg QD) for preventing the composite outcome of stroke or systemic embolism in patients with atrial fibrillation and at least one additional risk factor
  • Time Frame: Time to first occurrence
    Safety Issue?: No

Secondary Measures

• To determine, in the same patients, if apixaban is superior to ASA for prevention of the composite outcome of: Stroke, systemic embolism, myocardial infarction or vascular death (major vascular events)
  • Time Frame: Time to first occurrence
    Safety Issue?: No

Inclusion Criteria:

• Permanent or persistent atrial fibrillation documented by 12 lead ECG on the day of screening
• Presence of at least one of the following risk factors for stroke:
• Prior stroke or TIA
• Age ≥ 75 years
• Arterial hypertension on treatment
• Diabetes mellitus
• Heart failure. NYHA Class 2 or greater at time of enrollment
• Left ventricular ejection fraction 35% or less, documented within 6 months of enrollment
• Documented peripheral arterial disease (previous arterial revascularization, limb or foot amputation, or current intermittent claudication with ankle-arm systolic blood pressure ratio < 0.9)
• The patient is not currently receiving vitamin K antagonist therapy for one of the following reasons:
• Previous vitamin K antagonist therapy has been demonstrated to be unsuitable and its use has been discontinued (e.g., poor anticoagulant control, adverse events, need for other treatments that may interact with VKA, patient unable or unwilling to adhere to dose or INR monitoring instructions)
• Vitamin K antagonist therapy has not been previously used but would be expected to be unsuitable (e.g., unlikely to comply with dosing or monitoring requirement, need for other treatments which may interact with VKA, unlikely to adhere to restrictions on alcohol, diet or non-prescription medications, risk of VKA therapy considered to outweigh the risk of stroke or systemic embolism, patient is unwilling to take VKA).
• Men and women ≥ 50 years of age

Exclusion Criteria:

• Women who are pregnant or breast feeding
• Conditions other than atrial fibrillation that require chronic anticoagulation (e.g., prosthetic mechanical heart valve, venous thromboembolism; also see section 5.5
• Concomitant Treatments)
• Patient with serious bleeding in the last 6 months or at high risk of bleeding. This includes, but is not limited to:
• Active peptic ulcer disease
• Platelet count < 100,000/mm3 or hemoglobin < 10g/dL
• Recent stroke (within 10 days)
• Documented hemorrhagic tendencies or blood dyscrasias
• Current alcohol or drug abuse, or psychosocial reasons that make study participation impractical
• Severe co-morbid condition with life expectancy <1 year
• Severe renal insufficiency (serum creatinine > 2.5 mg/dL [221 umol/L] or a calculated creatinine clearance < 25 ml/min)
• ALT or AST > 2 times upper limit of normal or a total bilirubin > 1.5 times upper limit of normal (unless an alternative causative factor [e.g., Gilbert's syndrome] is identified)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 50 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Bristol-Myers Squibb

Overall Clinical Trial Officials and Contacts

Bristol-Myers Squibb Study Director Bristol-Myers Squibb  

Overall Contact: For participation information at a USA site use a phone number below. For site information outside the USA please email:  Clinical.Trials@bms.com

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00496769

Study ID Number: CV185-048

ClinicalTrials.gov Identifier: NCT00496769

Health Authority: United States: Food and Drug Administration

BMS Clinical Trials Disclosure

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm