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

Completed

Phase 3 Results

Trial Description

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).

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.

Conditions

Interventions

  • Warfarin (Coumadin┬«)Drug
    Other Names: Coumadin; Acenocoumarol
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: 001
    Description: Rivaroxaban placebo Equal number of rivaroxaban placebo tablets up for up to an expected maximum treatment period of 32 months that may extend up to 4 years,Warfarin Number of warfarin tablets to be determined by dose based on target INR values once daily for up to an expected maximum treatment period of 32 months that may extend up to 4 years
    ARM 2: Kind: Experimental
    Label: Warfarin
  • Rivaroxaban Drug
    Intervention Desc: 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)
    ARM 1: Kind: Experimental
    Label: 002
    Description: Rivaroxaban One 20 mg tablet once daily (one 15 mg tablet once daily in patients with moderate renal impairment) for up to an expected maximum treatment period of 32 months that may extend up to 4 years,Warfarin placebo 1 warfarin placebo tablet for up to an expected maximum treatment period of 32 months that may extend up to 4 years
    ARM 2: Kind: Experimental
    Label: Rivaroxaban
  • Warfarin placebo Drug
    Intervention Desc: 1 warfarin placebo tablet for up to an expected maximum treatment period of 32 months that may extend up to 4 years
    ARM 1: Kind: Experimental
    Label: 002
    Description: Rivaroxaban One 20 mg tablet once daily (one 15 mg tablet once daily in patients with moderate renal impairment) for up to an expected maximum treatment period of 32 months that may extend up to 4 years,Warfarin placebo 1 warfarin placebo tablet for up to an expected maximum treatment period of 32 months that may extend up to 4 years
  • Rivaroxaban placebo Drug
    Intervention Desc: Equal number of rivaroxaban placebo tablets up for up to an expected maximum treatment period of 32 months that may extend up to 4 years
    ARM 1: Kind: Experimental
    Label: 001
    Description: Rivaroxaban placebo Equal number of rivaroxaban placebo tablets up for up to an expected maximum treatment period of 32 months that may extend up to 4 years,Warfarin Number of warfarin tablets to be determined by dose based on target INR values once daily for up to an expected maximum treatment period of 32 months that may extend up to 4 years
  • Matching placebo for Rivaroxaban arm (Warfarin placebo) Drug
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: Rivaroxaban
  • Matching placebo for Warfarin arm (Rivaroxaban placebo) Drug
    Intervention Desc: 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
    ARM 1: Kind: Experimental
    Label: Warfarin

Trial Design

  • Allocation: Randomized
  • Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
  • Purpose: Prevention
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Patient Involvement

Patients are randomly assigned to receive rivaroxaban 20 mg od or dose adjusted warfarin (international normalized ratio [INR] 2.0-3.0). Patients and investigators utilize point-of-care INR devices to receive true or sham INR values, depending on the study drug allocation.

Outcomes

Type Measure Time Frame Safety Issue
Primary Composite of major and non-major clinically relevant bleeding events; any stroke or non-CNS systemic embolism.
Secondary Each category of bleeding events, and adverse events; composite of stroke, non-CNS systemic embolism, and vascular death.
Primary The composite of stroke and non-CNS systemic embolism Up to 4 years No
Secondary The composite of stroke, non-CNS systemic embolism, and vascular death Up to 4 years No
Primary The Composite Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Non-Inferiority) Up to 4 years No
Primary The Composite of Event of Stroke/Non-CNS Systemic Embolism: Primary Efficacy (Superiority) Up to 4 years No
Primary The Composite Event of Major/Non-major Clinically Relevant Bleeding Events: Primary Safety Up to 4 years No
Secondary The Composite Event of Stroke/Non-CNS Systemic Embolism/Vascular Death Up to 4 years No
Secondary The Composite Event of Stroke/Non-CNS Systemic Embolism/Myocardial Infarction/Vascular Death Up to 4 years No
Secondary The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Stroke Up to 4 years No
Secondary The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Non-CNS Systemic Embolism Up to 4 years No
Secondary The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Myocardial Infarction Up to 4 years No
Secondary The Individual Components of the Composite Primary and Major Secondary Efficacy Outcome Measures: Vascular Death Up to 4 years No
Secondary All-cause Mortality Up to 4 years No

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