Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation "EngageAFTIMI48"

Completed

Phase 3 Results

Trial Description

This study is to demonstrate the safety and efficacy profile, in two different dose regimens of Edoxaban (DU-176b), (an investigational new drug being tested for the prevention of stroke/systemic embolic events (SEE)), in individuals with atrial fibrillation. Patients will be randomized to one of three treatment groups: High Dose Regimen, Low Dose Regimen, & Warfarin. The expected duration of the study is 24 months.

Conditions

Interventions

  • Warfarin (Coumadin┬«)Drug
    Other Names: Coumadin; Acenocoumarol
    Intervention Desc: Anticoagulant (Vitamin K antagonist)
  • DU176b Drug
    Intervention Desc: DU-176b is an oral anticoagulant that directly inhibits Factor Xa, a clotting factor in the blood.
  • Warfarin tablets Drug
    Intervention Desc: Warfarin tablets plus Edoxaban placebo tablets each taken once daily for 24 months
    ARM 1: Kind: Experimental
    Label: 1
    Description: Warfarin tablets plus placebo DU-176b tablets
    ARM 2: Kind: Experimental
    Label: Warfarin/placebo edoxaban
    Description: Warfarin tablets plus placebo Edoxaban tablets
  • DU-176b tablets (high dose regimen) Drug
    Intervention Desc: DU-176b tablets plus warfarin placebo tablets each taken once daily for 24 months
    ARM 1: Kind: Experimental
    Label: 2
    Description: DU-176b tablets plus warfarin placebo tablets
  • DU-176b tablets (low dose regimen) Drug
    Intervention Desc: DU-176b tablets plus warfarin placebo tablets each taken once daily for 24 months
    ARM 1: Kind: Experimental
    Label: 3
    Description: DU-176b tablets plus warfarin placebo tablets
  • Edoxaban tablets (high dose regimen) Drug
    Intervention Desc: Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months
    ARM 1: Kind: Experimental
    Label: 2
    Description: Edoxaban tablets plus warfarin placebo tablets
  • Edoxaban tablets (low dose regimen) Drug
    Intervention Desc: Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months
    ARM 1: Kind: Experimental
    Label: 3
    Description: Edoxaban tablets plus warfarin placebo tablets
  • Edoxaban tablets (high dose regimen-60mg) Drug
    Intervention Desc: Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months
    ARM 1: Kind: Experimental
    Label: high dose edoxaban/placebo warfarin
    Description: Edoxaban tablets (60mg) plus warfarin placebo tablets
  • Edoxaban tablets (low dose regimen-30mg) Drug
    Intervention Desc: Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months
    ARM 1: Kind: Experimental
    Label: low dose edoxaban/placebo warfarin
    Description: Edoxaban tablets (30mg) plus warfarin placebo tablets
  • Placebo warfarin Drug
    Intervention Desc: placebo warfarin
    ARM 1: Kind: Experimental
    Label: high dose edoxaban/placebo warfarin
    Description: Edoxaban tablets (60mg) plus warfarin placebo tablets
    ARM 2: Kind: Experimental
    Label: low dose edoxaban/placebo warfarin
    Description: Edoxaban tablets (30mg) plus warfarin placebo tablets
  • Placebo edoxaban Drug
    Intervention Desc: placebo edoxaban
    ARM 1: Kind: Experimental
    Label: Warfarin/placebo edoxaban
    Description: Warfarin tablets plus placebo Edoxaban tablets

Trial Design

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

Patient Involvement

Patients will be randomized to one of three treatment groups: High Dose Regimen, Low Dose Regimen, & Warfarin. The expected duration of the study is 24 months.

Outcomes

Type Measure Time Frame Safety Issue
Primary The primary objective is to compare DU-176b to warfarin with regard to the composite primary endpoint of stroke and systemic embolic events.
Secondary To compare DU-176b to warfarin with regard to the composite clinical outcome of stroke, systemic embolic events, and all-cause mortality; to compare DU-176b to warfarin with regard to major bleeding events.
Secondary To compare DU-176b to warfarin with regard to the composite clinical outcome of stroke, SEE, and all-cause mortality 24 Months No
Secondary To compare DU-176b to warfarin with regard to major bleeding events 24 Months Yes
Primary The primary objective is to compare Edoxaban to warfarin with regard to the composite primary endpoint of stroke and systemic embolic events. 24 Months No
Secondary To compare Edoxaban to warfarin with regard to the composite clinical outcome of stroke, SEE, and all-cause mortality 24 Months No
Secondary To compare Edoxaban to warfarin with regard to major bleeding events 24 Months Yes
Secondary To compare Edoxaban to warfarin with regard to the composite clinical outcome of stroke, SEE, and all-cause mortality, as well as each component separately. 24 Months No
Secondary To compare Edoxaban to warfarin with regard to major bleeding as well as major plus clinically relevant non-major bleeding 24 Months Yes
Secondary To compare Edoxaban to warfarin with regard to the composite clinical outcome of stroke, SEE, and CV mortality, as well as each component separately 24 months No
Secondary To compare Edoxaban to warfarin with regard to MACE, defined for this Phase 3 study as a composite of non-fatal MI, non-fatal stroke, non-fatal SEE, and death due to CV cause or bleeding, as well as each component separately 24 months No
Primary Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up No
Primary Compare Edoxaban to Warfarin for Superiority for Composite of Stroke and Systemic Embolic Events (SEE). overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up No
Secondary Compare Edoxaban to Warfarin for Composite of Stroke, Systemic Embolic Event (SEE), and Cardiovascular (CV) Mortality overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up No
Secondary Compare Edoxaban to Warfarin for Major Adverse Cardiac Event (MACE): a Composite of Non-fatal MI, Non-fatal Stroke, Non-fatal SEE, and Death Due to CV Cause or Bleeding overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up No
Secondary Compare Edoxaban to Warfarin for Composite of Stroke, SEE, and All-cause Mortality overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up No
Secondary Adjudicated Bleeding Events on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up Yes

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