The purpose of this clinical research study is to learn if apixaban is moreeffective than Acetylsalicylic Acid (ASA) in preventing strokes associatedwith subjects who have atrial fibrillation. The safety of this treatmentwill also be studied

Phase 1

• Conditions: Patients with atrial fibrillation and at least one additional risk factor for stroke who have failed or are unsuitable for vitamin K antagonist therapy.; MedDRA version: 17.1Level: LLTClassification code 10042244Term: StrokeSystem Organ Class: 100000004852; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2007-001557-26-PL
• Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-30
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 6160

Inclusion Criteria

1) a) Signed written informed consent form

2) Target Population
b) 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 ECG, 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.
c) 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)
d) 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 nonprescription
medications, risk of VKA therapy considered to outweigh
the risk of stroke or systemic embolism, patient is unwilling to take
VKA).
3) Age and Sex
e) Men and women = 50 years of age

LONG TERM OPEN LABEL EXTENSION

1) Signed Written Informed
a) All subjects must provide signed written informed consent to participate in the
Long-Term Open-Label Extension
2) Target Population
a) All subjects must be receiving double-blind study medication (i.e., not having
permanently or temporarily [for >30 days] discontinued study medication) at the
time they present for their last double-blind study visit (Month 36/EOT).

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 1478
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4682

Exclusion Criteria

1) Sex and reproductive status
a) Women who are pregnant or breast feeding
b) Women of child bearing potential (WOCBP) who are unwilling to meet the study
requirements for pregnancy testing (see section 7.6.1 Requirements for Pregnancy
Testing) or are unwilling or unable to use an acceptable method to avoid
pregnancy.
WOCBP includes any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or> 12 consecutive months; or women on hormone replacement therapy (HRT) with
documented serum follicle stimulating hormone (FSH) level > 35 m IU/ml]. Even
women who are using oral contraceptives, other hormonal contraceptives (vaginal
products, skin patches, or implanted or injectable products), or mechanical products
such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides)
to prevent pregnancy, or are practicing abstinence or where their partner is sterile
(e.g., vasectomy) should be considered of child bearing potential.
2) Target Disease Exceptions
c) Atrial fibrillation due to reversible causes (e.g. thyrotoxicosis, pericarditis)
d) Valvular disease requiring surgery
e) Planned atrial fibrillation ablation procedure to be performed within 3 months.
3) Medical History and Concurrent Disease
f) Conditions other than atrial fibrillation that require chronic anticoagulation (e.g.,
prosthetic mechanical heart valve, venous thromboembolism; also see section 5.5
Concomitant Treatments).
g) 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
h) Current alcohol or drug abuse, or psychosocial reasons that make study
participation impractical
i) Severe co-morbid condition with life expectancy <1 year
4) Physical and Laboratory Test Findings
j) Severe renal insufficiency ( 2.5 mg/dL [221 umol/L] or a
calculated creatinine clearance < 25 ml/min is excluded)
k) 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)
5) Allergies and Adverse Drug Reactions
Allergy or adverse reaction to ASA
6) Prohibited Treatments and/or Therapies
l) See section 5.5.1 (Prohibited and/or Restricted Treatments) for therapies which
are prohibited at study entry
m) Required treatment with a thienopyridine (clopidogrel or ticlopidine; see also
section 5.5.2.1 Acetylsalicylic acid (ASA) and Thienopyridines).
7) Other Exclusion Criteria
n) Prisoners or subjects who are compulsorily detained (involuntarily incarcerated)
o) Use of an investigational drug or device within the past 30 days or prior
randomization into an apixaban clinical study
p) Patients who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness
Eligibility criteria for this study have been carefully considered to ensure the safety of
study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.

LONG TERM OPEN LABEL EXTENSION
a) No exclusion criterion for the double-blind

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified