A Phase III Study of Apixaban in Patients With Atrial Fibrillation

• Register: ClinicalTrials.gov
• Last refreshed on: 4 March 2013
• Main ID: NCT00496769
• Date of registration: 02/07/2007
• Primary sponsor: Bristol-Myers Squibb
• Public title: A Phase III Study of Apixaban in Patients With Atrial Fibrillation AVERROES
• Scientific title: Apixaban Versus Acetylsalicylic Acid (ASA) to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment: A Randomized Double Blind Trial
• Date of first enrolment: September 2007
• Target sample size: 5600
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT00496769
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Countries of recruitment

Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Israel, Italy, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Philippines, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Bristol-Myers Squibb
• Affiliation: Bristol-Myers Squibb

Key inclusion & exclusion criteria

Inclusion Criteria:

- Permanent, paroxysmal or persistent atrial fibrillation documented by 12 lead ECG on
the day of screening OR

- If not in atrial fibrillation at screening, atrial fibrillation must be documented in
the 6 months prior to enrollment by 12 lead ECF, or as an episode at least 5 minutes
in duration on a rhythm strip or Holter recording. Pacemaker or ICD electrogram
recordings may be used to document AF but the duration of atrial fibrillation must be
at least 30 minutes if this is the only documentation of AF

- 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

- Women of child bearing potential (WOCBP) who are unwilling to meet the study
requirements for pregnancy testing or are unwilling or unable to use an acceptable
method to avoid pregnancy.

- Atrial fibrillation due to reversible causes (e.g., thyrotoxicosis, pericarditis)

- Valvular disease requiring surgery

- Planned atrial fibrillation ablation procedure to be performed within 3 months

- Conditions other than atrial fibrillation that require chronic anticoagulation (e.g.,
prosthetic mechanical heart valve, venous thromboembolism

- 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 (creatinine clearance must be calculated in all
patients: any patient with either a serum creatinine > 2.5 mg/dL [221 umol/L] or
a calculated creatinine clearance < 25 ml/min is excluded)

- 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)

- Allergy or adverse reaction to ASA

- See section 5.5.1 (Prohibited and/or Restricted Treatments) for therapies which are
prohibited at study entry

- Required treatment with a thienopyridine (clopidogrel or ticlopidine; see also
section 5.5.2.1 Acetylsalicylic acid (ASA) and Thienopyridines).

- Prisoners or subjects who are compulsory detained (involuntarily incarcerated)

- Use of an investigational drug or device within the past 30 days or prior
randomization into an apixaban clinical study

- Patients who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness



Age minimum: 50 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Atrial Fibrillation

Intervention(s)

Drug: Acetylsalicylic Acid (ASA)

Drug: Apixaban

Primary Outcome(s)

The primary efficacy outcome will be the time (days) from first dose of study drug to first occurrence of unrefuted ischemic stroke, hemorrhagic stroke or systemic embolism [Time Frame: Time to first occurrence]

Secondary Outcome(s)

The secondary efficacy outcome will be the time (days) from first dose of study drug to first occurrence of unrefuted Ischemic stroke, hemorrhagic stroke, systemic embolism, myocardial infarction, or vascular death [Time Frame: Time to first occurrence]

Secondary ID(s)

CV185-048

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Pfizer