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 Amendments 02, 05,07, 10 & 11 and Administrative 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-DK

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

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. documented peptic ulcer disease within 6 months, 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 stroke (within 30 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 < 10 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 the integrity of the study data. It is imperative that subjects fully meet all eligibility criteria.
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.