Protocol Title: A Phase 3, Active (Warfarin) Controlled, Randomized, Double-Blind,Parallel Arm Study to Evaluate Efficacy and Safety of Apixaban in Preventing Strokeand Systemic Embolism in Subjects with Nonvalvular Atrial Fibrillation - ARISTOTLE

• Conditions: Thrombosis; Arrhythmia; Level: PTClassification code 10003658

• Registration Number: EUCTR2006-002147-91-IT
• Lead Sponsor: Bristol_myers Squibb International Corporation

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10-08
• Last Update Posted: 17 July 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 15000

Inclusion Criteria

For entry into the study, the following criteria MUST be met.

1) Age ≥ 18 years

2) Permanent or persistent atrial fibrillation or atrial flutter 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 at least 2 weeks apart in the 6

months prior to enrollment. Atrial fibrillation/flutter may be documented by ECG, or as

an episode at least one minute in duration on a rhythm strip or Holter recording.

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 are practicing 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. 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, See Section 6.3.2.2)

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.

Study & Design

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