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
  Purpose

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.


Condition Intervention Phase
Stroke
Atrial Fibrillation
Embolism
Drug: warfarin tablets
Drug: Edoxaban tablets (high dose regimen-60mg)
Drug: Edoxaban tablets (low dose regimen-30mg)
Drug: placebo warfarin
Drug: placebo edoxaban
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 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)

Resource links provided by NLM:


Further study details as provided by Daiichi Sankyo Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.



Enrollment: 21105
Study Start Date: November 2008
Study Completion Date: May 2013
Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Warfarin/placebo edoxaban
Warfarin tablets plus placebo Edoxaban tablets
Drug: warfarin tablets
Warfarin tablets plus Edoxaban placebo tablets each taken once daily for 24 months
Drug: placebo edoxaban
placebo edoxaban
Experimental: high dose edoxaban/placebo warfarin
Edoxaban tablets (60mg) plus warfarin placebo tablets
Drug: Edoxaban tablets (high dose regimen-60mg)
Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months
Drug: placebo warfarin
placebo warfarin
Experimental: low dose edoxaban/placebo warfarin
Edoxaban tablets (30mg) plus warfarin placebo tablets
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

  Eligibility

Ages Eligible for Study:   21 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00781391

  Show 1017 Study Locations
Sponsors and Collaborators
Daiichi Sankyo Inc.
The TIMI Study Group
  More Information

No publications provided by Daiichi Sankyo Inc.

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

Responsible Party: Daiichi Sankyo Inc.
ClinicalTrials.gov Identifier: NCT00781391     History of Changes
Other Study ID Numbers: DU176b-C-U301
Study First Received: October 28, 2008
Results First Received: February 5, 2015
Last Updated: March 12, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Daiichi Sankyo Inc.:
Systemic embolic events

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

ClinicalTrials.gov processed this record on July 30, 2015