Efficacy and Safety of Rivaroxaban for the Prevention of Stroke in Subjects With Non-Valvular Atrial Fibrillation

This study has been completed.
Sponsor:
Collaborator:
Janssen R&D, L.L.C.
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00494871
First received: June 29, 2007
Last updated: March 17, 2014
Last verified: March 2014
  Purpose

This is a clinical study evaluating the efficacy and safety of rivaroxaban for stroke prevention in patients with atrial fibrillation (originally described in Japanese).


Condition Intervention Phase
Atrial Fibrillation
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Drug: Warfarin
Drug: Rivaroxaban placebo
Drug: Warfarin placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Evaluation of the Efficacy and Safety of Rivaroxaban (BAY59-7939) for the Prevention of Stroke and Non-central Nervous System Systemic Embolism in Subjects With Non-valvular Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Event Rate of the Composite Endpoint of Adjudicated Major Bleeding or Adjudicated Non-major Clinically Relevant Bleeding [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: Yes ]
    Major bleeding: clinically overt bleeding (COB) associated with a fall in hemoglobin ≥2 g/dL, leading to transfusion ≥2 units of packed red blood cells or whole blood, occurring in a critical site or contributing to death. Non-major clinically relevant bleeding: COB that does not meet the definition of major bleeding, but requires medical intervention or unscheduled contact with the physician, (temporary) discontinuation of the study treatment, discomfort to the subject such as pain, or impairment of activities of daily life.


Secondary Outcome Measures:
  • Event Rate of the Composite Endpoint of Adjudicated Stroke and Non-central Nervous System (CNS) Systemic Embolism [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    This is the principal efficacy endpoint. Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded.

  • Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, and Vascular Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded. Any death that was not clearly non-vascular.

  • Event Rate of the Composite Endpoint of Adjudicated Stroke, Non-CNS Systemic Embolism, Myocardial Infarction, and Vascular Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    Stroke included hemorrhagic, ischemic infarction and unknown. Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded. Myocardial infarction: assessed based on either cardiac biomarkers, new abnormal Q waves appeared on electrocardiogram for ≥2 leads, or autopsy confirmation. Any death that was not clearly non-vascular.

  • Event Rate of Stroke [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. Stroke included hemorrhagic (Stroke with local collections of intraparenchymal blood. Subarachnoid hemorrhage, subdural hemorrhage, and epidural hemorrhage were excluded.), ischemic infarction (Stroke without focal collection of intracranial blood) and unknown (No imaging data and anatomic findings were available.).

  • Event Rate of Non-CNS Systemic Embolism [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. Non-CNS systemic embolism was abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion in the absence of other likely mechanisms (such as trauma, atherosclerosis, and instrumentation). Arterial emboli in the following areas were "non-CNS systemic embolism": peripheral arterial in the upper and lower extremities, renal, mesenteric, splenic, hepatic, ocular/retinal and others. Pulmonary embolism or myocardial infarction was excluded from this category.

  • Event Rate of Myocardial Infarction [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. Myocardial infarction was assessed based on either cardiac bio-markers (troponin I, troponin T, or creatine kinase-muscle and brain subunit isozyme), new abnormal Q waves appeared on ECG for 2 or more leads, or autopsy confirmation.

  • Event Rate of Vascular Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. Any death that was not clearly non-vascular (e.g., deaths due to spontaneous bleeding, myocardial infarction, stroke, cardiac failure, and arrhythmia)

  • Event Rate of Stroke With Serious Residual Disability [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. A stroke was considered disabling if the participant's modified Rankin score was between 3 and 5, inclusive.

  • Event Rate of All-cause Death [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: No ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. All-cause death included vascular death and non-vascular death.

  • Event Rate of Adjudicated Major Bleeding [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: Yes ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. Major bleeding was clinically overt bleeding associated with a fall in hemoglobin of 2 g/dL or higher, leading to a transfusion of 2 or more units of packed red blood cells or whole blood, occurring in a critical site or contributing to death.

  • Event Rate Adjudicated Non-major Clinically Relevant Bleeding [ Time Frame: Up to 2 days after the last dose ] [ Designated as safety issue: Yes ]
    All events were adjudicated and confirmed by a central independent committee blinded to treatment. Non-major clinically relevant bleeding was clinically overt bleeding that does not meet the definition of major bleeding, but requires medical intervention or unscheduled contact with the physician, (temporary) discontinuation of the study treatment, discomfort to the subject such as pain, or impairment of activities of daily life.


Enrollment: 1280
Study Start Date: June 2007
Study Completion Date: January 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban (Xarelto, BAY59-7939)
Participants received once daily (OD) a rivaroxaban 15 mg tablet and a warfarin placebo tablet during the double-blind treatment period
Drug: Rivaroxaban (Xarelto, BAY59-7939)
Participants orally administered rivaroxaban 15 mg OD (CrCL [creatinine clearance] >= 50 mL/min) or 10 mg OD (CrCL 30-49 mL/min)
Drug: Warfarin placebo
Participants orally administered a warfarin placebo tablet (adjusted based upon sham INR values)
Active Comparator: Warfarin
Participants received OD a warfarin potassium tablet and a rivaroxaban placebo tablet during the double-blind treatment period
Drug: Warfarin
Participants orally administered a warfarin potassium tablet (INR [international normalized ratio] target was 1.6-2.6 for patients >70 years and 2.0-3.0 for patients <70 years)
Drug: Rivaroxaban placebo
Participants orally administered a rivaroxaban placebo tablet

Detailed Description:

Within the US 'Johnson & Johnson Pharmaceutical Research & Development, L.L.C.' is sponsor.

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 20 years or older
  • Japanese male or female
  • Non- valvular atrial fibrillation documented by ECG
  • Patients with a risk of stroke and non-CNS systemic embolism

Exclusion Criteria:

  • Significant mitral stenosis
  • Patients in whom anticoagulants are contraindicated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00494871

  Show 165 Study Locations
Sponsors and Collaborators
Bayer
Janssen R&D, L.L.C.
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00494871     History of Changes
Other Study ID Numbers: 12620
Study First Received: June 29, 2007
Results First Received: March 28, 2012
Last Updated: March 17, 2014
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Bayer:
BAY59-7939
Rivaroxaban
Non-Valvular Atrial Fibrillation
Japanese Patients
Phase III
12620

Additional relevant MeSH terms:
Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014