A Prospective, Randomized, Double-Blind, Double-Dummy, Parallel-Group, Multicenter, Event-Driven, Non-inferiority Study Comparing the Efficacy and Safety of Once Daily Oral Rivaroxaban (BAY 59-7939) With Adjusted-Dose Oral Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Subjects With Non-Valvular Atrial Fibrillation (39039039AFL3001)

Conditions: Prevention of Stroke and Non-CNS Systemic Embolism in Non-Valvular Atrial Fibrillation
MedDRA version: 8.1Level: LLTClassification code 10003658Term: Atrial fibrillation

Registration Number: EUCTR2006-004595-13-DE

Lead Sponsor: Bayer HealthCare AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 14000

Inclusion Criteria

Subjects must satisfy the following criteria to be enrolled in the study:
-Men or women aged =18 years with non-valvular atrial fibrillation
-Atrial fibrillation must be documented by ECG evidence (e.g., 12-lead ECG, rhythm strip, Holter, pacemaker interrogation) within 30 days before randomization. In addition, subjects must have medical evidence of atrial fibrillation within 1 year before and at least one day before the qualifying ECG evidence. This could be obtained from a notation in the subject's record (e.g., medical chart, hospital discharge summary).
Subjects with newly diagnosed atrial fibrillation are eligible provided that:
– there is evidence that the atrial fibrillation is non-valvular
– cardioversion is not planned
– there is ECG evidence on 2 occasions 24 hours apart demonstrating atrial fibrillation
- History of prior ischemic stroke, TIA or non-CNS systemic embolism believed to be cardioembolic in origin or has 2 or more of the following risk factors:
- Heart failure and/or left ventricular ejection fraction = 35%
- Hypertension (defined as use of antihypertensive medications within
6 months before the screening visit or persistent systolic blood pressure
above 140 mmHg or diastolic blood pressure above 90 mmHg)
- Age =75 years
- Diabetes mellitus (defined as a history of type 1 or type 2 diabetes
mellitus or use of antidiabetic medications within 6 months before
screening visit)
- Female subjects must be postmenopausal (for at least 2 years), surgically sterile, abstinent, or, if sexually active, be practicing an effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, intrauterine device, double-barrier method, contraceptive patch, male partner sterilization) before entry and throughout the study; and, for those of childbearing potential, have a negative serum ß-hCG pregnancy test at screening.
- Subjects must have signed an informed consent document
- In order to participate in the optional pharmacogenomic component, subjects must have signed the informed consent for DNA research document indicating willingness to participate in the pharmacogenomic component of the study (where local regulations permit)
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

Potential subjects who meet any of the following criteria will be excluded from participating in the study:
Cardiac-Related Conditions
- Hemodynamically significant mitral valve stenosis
- Prosthetic heart valve
- Planned cardioversion (electrical or pharmacological)
- Transient atrial fibrillation caused by a reversible disorder (e.g., thyrotoxicosis, PE, recent surgery, MI)
- Known presence of atrial myxoma or left ventricular thrombus
- Active endocarditis

Hemorrhage Risk-Related Criteria
- Active internal bleeding
- History of or condition associated with increased bleeding risk including, but not limited to:
- Major surgical procedure or trauma within 30 days before the
randomization visit
- Clinically significant gastrointestinal bleeding within 6 months before the
randomization visit
- History of intracranial, intraocular, spinal, or atraumatic intra-articular
bleeding
- Chronic hemorrhagic disorder
- Known intracranial neoplasm, arteriovenous malformation, or aneurysm
- Planned invasive procedure with potential for uncontrolled bleeding, including major surgery
- Platelet count <90,000/µL at the screening visit
- Sustained uncontrolled hypertension: systolic blood pressure =180 mmHg or diastolic blood pressure =100 mmHg

Concomitant Conditions and Therapies
- Severe, disabling stroke (modified Rankin score of 3 to 5, inclusive) within 6 months or any stroke within 30 days before the randomization visit
- Transient ischemic attack within 3 days before the randomization visit
- Indication for anticoagulant therapy for a condition other than atrial fibrillation (e.g., VTE)
Treatment with:
– Aspirin >100 mg daily
– Aspirin in combination with thienopyridines within 5 days before randomization
– Intravenous antiplatelets within 5 days before randomization
– Fibrinolytics within 10 days before randomization
– Note: Aspirin £100 mg monotherapy is allowed and thienopyridine monotherapy is allowed.
- Anticipated need for chronic treatment with a non steroidal anti inflammatory drug
- Systemic treatment with a strong inhibitor of cytochrome P450 3A4, such as ketoconazole or protease inhibitors, within 4 days before randomization, or planned treatment during the time period of the study
- Treatment with a strong inducer of cytochrome P450 3A4, such as rifampin/rifampicin, within 4 days before randomization, or planned treatment during the time period of the study
- Anemia (hemoglobin <10 g/dL) at the screening visit
- Pregnancy or breast feeding
- Any other contraindication to warfarin
- Known HIV infection at time of screening
- Calculated CLCR <30 mL/min at the screening visit
- Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis), or ALT >3 x the ULN

Study Participation and Follow-up-Related Criteria
- Serious concomitant illness associated with a life expectancy of less than 2 years
- Drug addiction or alcohol abuse within 3 years before the randomization visit
- Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment
- Previous randomization in the present study or other study of rivaroxaban
- Known allergy or hypersensitivity to any component of rivaroxaban, warfarin or placebo excipients (includes lactose, microcrystalline cellulose, magnesium stearate, hypromellose, macrogol, croscarmellose sodium, sodium lauryl sulfate, titanium oxide/f