A Phase 3, Active (Warfarin) Controlled, Randomized, Double-Blind, Parallel Arm Study to Evaluate Efficacy and Safety of Apixaban in Preventing Stroke and Systemic Embolism in Subjects with Nonvalvular Atrial Fibrillation + Pharmacogenetics Blood Sample Amendment Number 1 - Site Specific, version 3.0, dated 04-Nov-2006Revised protocol 04 incorporating Amdt 02, 05, 07,10 & 11 and Admin letters 02, 04, 05 & 08 - ARISTOTLE

Conditions: ARRHYTHMIA
THROMBOSIS
MedDRA version: 9.1Level: LLTClassification code 10003658Term: Atrial fibrillation
MedDRA version: 9.1Level: LLTClassification code 10057613Term: Thromboembolic stroke

Registration Number: EUCTR2006-002147-91-CZ

Lead Sponsor: Bristol Myers Squibb International Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 18000

Inclusion Criteria

For entry into the study, the following criteria MUST be met.
1) Age >= 18 years
2) In atrial fibrillation or atrial flutter not due to a reversible cause and documented by ECG at the time of enrollment.
OR
If not in atrial fibrillation/flutter at the time of enrollment, must have atrial
fibrillation/flutter documented on two separate occasions, not due to a reversible cause at least 2 weeks apart in the 12 months prior to enrollment. Atrial fibrillation/flutter may be documented by ECG, or as an episode lasting at least one minute on a rhythm strip or Holter recording or intercardiac electrogram (from an implanted pacemaker or defibrillator).
3) One or more of the following risk factor(s) for stroke:
a) Age 75 years or older
b) Prior stroke, TIA or systemic embolus
c) Either symptomatic congestive heart failure within 3 months or left ventricular
dysfunction with an LV ejection fraction (LVEF) =< 40% by echocardiography,
radionuclide study or contrast angiography
d) Diabetes mellitus
e) Hypertension requiring pharmacological treatment
4) Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the treatment period of the study or for
2 weeks after the last dose of study medication, whichever is longer, in such a manner that the risk of pregnancy is minimized.
WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal (defined as amenorrhea >= 12 consecutive months; or women on hormone replacement therapy [HRT] with documented serum follicle stimulating hormone [FSH] level > 35 mIU/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 arepracticing abstinence or where their partner is sterile (eg, vasectomy) should be
considered to be of childbearing potential.
WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25
IU/L or equivalent units of HCG) within 48 hours prior to the start of investigational
product.
5) All subjects must provide signed written informed consent.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1) Atrial fibrillation or flutter due to reversible causes (e.g. thyrotoxicosis, pericarditis)
2) Clinically significant (moderate or severe) mitral stenosis
3) Increased bleeding risk that is believed to be a contraindication to oral anticoagulation
(e.g. previous intracranial hemorrhage)
4) Conditions other than atrial fibrillation that require chronic anticoagulation (e.g.
prosthetic mechanical heart valve)
5) Persistent, uncontrolled hypertension (systolic BP > 180 mm Hg, or diastolic BP
> 100 mm Hg)
6) Active infective endocarditis
7) Planned major surgery
8) Planned atrial fibrillation or flutter ablation procedure
9) Use of an unapproved, investigational drug or device within the past 30 days
10) Required treatment with aspirin > 165 mg/day
11) Simultaneous treatment with both aspirin and a thienopyridine (e.g., clopidogrel,
ticlopidine)
12) Severe comorbid condition with life expectancy of =< 1 year
13) Active alcohol or drug abuse, or psychosocial reasons that make study participation
impractical
14) Recent ischemic stroke (within 7 days)
15) Severe renal insufficiency (serum creatinine > 2.5 mg/dL or a calculated creatinine
clearance < 25 mL/min)
16) ALT or AST > 2X ULN or a Total Bilirubin >= 1.5X ULN (unless an alternative
causative factor [e.g., Gilbert’s syndrome] is identified)
17) Platelet count =< 100,000/ mm3
18) Hemoglobin < 9 g/dL
19) Inability to comply with INR monitoring
20) Prior randomization into an apixaban clinical study
21) Prisoners or subjects who are involuntarily incarcerated
22) Subjects who are compulsorily detained for treatment of either a psychiatric or
physical (e.g., infectious disease) illness
23) Women of child bearing potential (WOCBP) unwilling or unable to use an acceptable
method to avoid pregnancy:
a) WOCBP using a prohibited contraceptive method
b) WOCBP include any female who has experienced menarche and who has not
undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation,
or bilateral oophorectomy) or is not postmenopausal [defined as amenorrhea >= 12
consecutive months; or women on hormone replacement therapy (HRT) with
documented serum follicle stimulating hormone (FSH) level > 35 mIU/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 to be of child bearing
potential
c) Women who are pregnant or breastfeeding
d) Women with a positive pregnancy test on enrollment or prior to administration of
investigational product.
Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria.