An Efficacy and Safety Study of Rivaroxaban With Warfarin for the Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients With Non-Valvular Atrial Fibrillation

This study has been completed.
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00403767
First received: November 23, 2006
Last updated: April 10, 2014
Last verified: April 2014
  Purpose

The purpose of this study is to compare the efficacy and safety of rivaroxaban with warfarin for the prevention of blood clots in the brain (referred to as stroke) and blood clots in other parts of the body referred to as non-central nervous system systemic embolism) in patients with non-valvular atrial fibrillation (a heart rhythm disorder).


Condition Intervention Phase
Atrial Fibrillation
Stroke
Embolism
Drug: Rivaroxaban
Drug: Warfarin
Drug: Matching placebo for Rivaroxaban arm (Warfarin placebo)
Drug: Matching placebo for Warfarin arm (Rivaroxaban 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, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Prospective, Randomized, Double-Blind, Parallel-Group, Multicenter, Non-inferiority Study Comparing the Efficacy and Safety of Rivaroxaban (BAY 59-7939) With Warfarin 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 Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

  • The Composite of Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Superiority) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a stroke or non-CNS systemic embolism while on treatment (defined as the time interval from the first dose to the last dose of study drug plus 2 days). The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

  • The Composite Event of Major/Non-major Clinically Relevant Bleeding Events: Primary Safety [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a major or non-major clinically relevant bleeding event while on treatment. The statistical analysis is based on time from the first dose of study drug to the first occurrence of the event while on treatment.


Secondary Outcome Measures:
  • The Composite Event of Stroke/Non-CNS Systemic Embolism/Vascular Death [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

  • The Composite Event of Stroke/Non-CNS Systemic Embolism/Myocardial Infarction/Vascular Death [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a stroke, non-CNS systemic embolism, myocardial infarction, or vascular death while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

  • The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Stroke [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a stroke while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

  • The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Non-CNS Systemic Embolism [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a non-CNS systemic embolism while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

  • The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Myocardial Infarction [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the first occurrence of a myocardial infarction while on treatment. The statistical analysis is based on time from randomization to the first occurrence of the event while on treatment.

  • The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Vascular Death [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients with the occurrence of vascular death while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.

  • All-cause Mortality [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The number of patients who died due to any cause while on treatment. The statistical analysis is based on time from randomization to the event while on treatment.


Enrollment: 14269
Study Start Date: December 2006
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rivaroxaban Drug: Rivaroxaban
Type=exact number, unit=mg, number=20, form=tablet, route=oral use. One 20 mg tablet once daily for an expected maximum treatment period of up to 32 months that may extend up to 4 years (Patients with moderate renal impairment at screening willl have a dose adaptation to rivaroxaban 15 mg, orally, once daily for an expected maximum treatment period of up to 32 months that may extend up to 4 years)
Drug: Matching placebo for Rivaroxaban arm (Warfarin placebo)
Form=tablet, route=oral. One warfarin placebo tablet taken orally once daily for up to an expected maximum treatment period of 32 months that may extend up to 4 years
Active Comparator: Warfarin Drug: Warfarin
Type=exact number, unit=mg, number=1, 2.5, or 5 mg, form=tablet, route=oral use. Number of warfarin tablets to be determined based on target INR values once daily for an expected maximum treatment period of up to 32 months that may extend up to 4 years
Drug: Matching placebo for Warfarin arm (Rivaroxaban placebo)
Form-tablet, Route=oral administration. Number of rivaroxaban placebo determined by the number of warfarin tablets taken. Duration of treatment is up to an expected maximum treatment period of 32 months that may extend up to 4 years

Detailed Description:

Patients with non-valvular atrial fibrillation who are at risk for stroke and non-central nervous system (non-CNS) systemic embolism, will be randomized (assigned by chance) to receive treatment with rivaroxaban or warfarin, two different anticoagulants (substances that prevent blood clots). Treatment will be double-blinded (neither the patient nor study staff will know which study drug is assigned to patients during the study). Patients assigned to rivaroxaban will receive rivaroxaban 20 mg orally (p.o.) once daily (OD) plus warfarin placebo p.o. OD titrated to a target sham international normalized ratio (INR) of 2.5. Patients with moderate renal impairment at screening will receive rivaroxaban 15 mg p.o. OD. Patients assigned to warfarin will receive warfarin p.o. OD titrated to a target INR of 2.5 plus rivaroxaban placebo p.o. OD. The maximum expected length of treatment is up to 32 months but may be extended up to 4 years.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have documented atrial fibrillation on 2 separate occasions within 6 months before screening
  • History of a prior stroke, transient ischemic attack or non-neurologic systemic embolism believed to be cardiac in origin, or at least two of the following risk factors: heart failure, hypertension, age 75 years or greater, diabetes mellitus

Exclusion Criteria:

  • Significant mitral stenosis
  • Transient atrial fibrillation caused by a reversible disorder
  • Active internal bleeding
  • Severe disabling stroke
  • History of intracranial bleeding
  • Hemorrhagic disorders
  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: NCT00403767

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Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Bayer
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

No publications provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier: NCT00403767     History of Changes
Other Study ID Numbers: CR012157, 39039039AFL3001, ROCKET AF, 2006-004595-13
Study First Received: November 23, 2006
Results First Received: December 2, 2011
Last Updated: April 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Atrial Fibrillation
Stroke
Embolism
Non-central nervous system systemic embolism
Non-valvular atrial fibrillation
Blood Clot
Rivaroxaban
Warfarin
Anticoagulants
Arrhythmias, Cardiac

Additional relevant MeSH terms:
Atrial Fibrillation
Embolism
Stroke
Cerebral Infarction
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Brain Infarction
Brain Ischemia
Rivaroxaban
Warfarin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 20, 2014