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)

This study has been completed.
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier:
NCT00781391
First received: October 28, 2008
Last updated: March 12, 2015
Last verified: March 2015

October 28, 2008
March 12, 2015
November 2008
April 2013   (final data collection date for primary outcome measure)
  • Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). [ Time Frame: on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    The composite of stroke and Systemic Embolic Events (SEE) during the on treatment period in the mITT analysis population with a non-inferiority analysis.
  • Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    The composite of stroke and Systemic Embolic Events (SEE) during the overall study period in the mITT analysis population.
  • Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). [ Time Frame: on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    The composite of stroke and Systemic Embolic Events (SEE) during the on treatment period in the PP (per protocol) analysis set population.
  • Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE). [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    The composite of stroke and Systemic Embolic Events (SEE) during the overall study period in the PP (per protocol) analysis set population.
  • Compare Edoxaban to Warfarin for Superiority for Composite of Stroke and Systemic Embolic Events (SEE). [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    Compare edoxaban to warfarin for the composite of stroke and Systemic Embolic Events (SEE) during the overall study period in the ITT analysis set with a superiority analysis.
The primary objective is to compare DU-176b to warfarin with regard to the composite primary endpoint of stroke and systemic embolic events. [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00781391 on ClinicalTrials.gov Archive Site
  • Compare Edoxaban to Warfarin for Composite of Stroke, Systemic Embolic Event (SEE), and Cardiovascular (CV) Mortality [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    Compare edoxaban to warfarin for the composite of stroke, Systemic Embolic Events, and Cardiovascular mortality during the overall study period in the ITT analysis set.
  • 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 [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    Compare edoxaban to warfarin for Major Adverse Cardiac Event (MACE): a composite of non-fatal Myocardial Infarction, non-fatal stroke, non-fatal Systemic Embolic Events, and death due to Cardiovascular cause or bleeding during the overall study period in the ITT analysis set.
  • Compare Edoxaban to Warfarin for Composite of Stroke, SEE, and All-cause Mortality [ Time Frame: overall study period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: No ]
    Compare Edoxaban to warfarin for Composite of stroke, Systemic Embolic Events, and all-cause mortality during the overall study period in the ITT analysis set.
  • Adjudicated Bleeding Events [ Time Frame: on-treatment period 2.5 years of median study drug exposure and 2.8 year of median follow-up ] [ Designated as safety issue: Yes ]

    Compare edoxaban versus warfarin for Adjudicated Bleeding Events during the on-treatment period in the Safety Analysis set.

    Major bleeding was adjudicated by the Clinical Events Committee (CEC) and defined based on published guidance from the International Society on Thrombosis and Haemostasis (ISTH), with minor modifications for Hgb decrease and blood transfusion requirements.

  • To compare DU-176b to warfarin with regard to the composite clinical outcome of stroke, SEE, and all-cause mortality [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
  • To compare DU-176b to warfarin with regard to major bleeding events [ Time Frame: 24 Months ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation
A Phase 3, Randomized, Double-Blind, Double-Dummy, Parallel Group, Multi-Center, Multi-National Study for Evaluation of Efficacy and Safety of Edoxaban (DU-176b) Versus Warfarin In Subjects With Atrial Fibrillation - Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation (ENGAGE - AF TIMI - 48)

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.

Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
  • Stroke
  • Atrial Fibrillation
  • Embolism
  • Drug: warfarin tablets
    Warfarin tablets plus Edoxaban placebo tablets each taken once daily for 24 months
  • Drug: Edoxaban tablets (high dose regimen-60mg)
    Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months
  • Drug: Edoxaban tablets (low dose regimen-30mg)
    Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months
  • Drug: placebo warfarin
    placebo warfarin
  • Drug: placebo edoxaban
    placebo edoxaban
  • Active Comparator: Warfarin/placebo edoxaban
    Warfarin tablets plus placebo Edoxaban tablets
    Interventions:
    • Drug: warfarin tablets
    • Drug: placebo edoxaban
  • Experimental: high dose edoxaban/placebo warfarin
    Edoxaban tablets (60mg) plus warfarin placebo tablets
    Interventions:
    • Drug: Edoxaban tablets (high dose regimen-60mg)
    • Drug: placebo warfarin
  • Experimental: low dose edoxaban/placebo warfarin
    Edoxaban tablets (30mg) plus warfarin placebo tablets
    Interventions:
    • Drug: Edoxaban tablets (low dose regimen-30mg)
    • Drug: placebo warfarin

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
21105
May 2013
April 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 21 years of age or older; male or female.
  • Able to provide written informed consent.
  • History of documented AF within the prior 12 months
  • A moderate to high risk of stroke, as defined by CHADS2 index score of at least 2

Exclusion Criteria:

  • Transient atrial fibrillation secondary to other reversible disorders
  • Subjects with moderate or severe mitral stenosis, unresected atrial myxoma, or a mechanical heart valve
  • Subjects with any contraindication for anticoagulant agents;
  • Subjects with conditions associated with high risk of bleeding or have known or suspected hereditary or acquired bleeding disorders
  • Females of childbearing potential including the following:

    • Females with a history of tubal-ligation
    • Females less than 2 years post-menopausal
Both
21 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Croatia,   Czech Republic,   Denmark,   Estonia,   Finland,   France,   Germany,   Greece,   Guatemala,   Hungary,   India,   Israel,   Italy,   Japan,   Korea, Republic of,   Mexico,   Netherlands,   New Zealand,   Norway,   Peru,   Philippines,   Poland,   Portugal,   Romania,   Russian Federation,   Serbia,   Slovakia,   South Africa,   Spain,   Sweden,   Switzerland,   Taiwan,   Thailand,   Turkey,   Ukraine,   United Kingdom
 
NCT00781391
DU176b-C-U301
Yes
Daiichi Sankyo Inc.
Daiichi Sankyo Inc.
The TIMI Study Group
Not Provided
Daiichi Sankyo Inc.
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP