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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00781391
Recruitment Status : Completed
First Posted : October 29, 2008
Results First Posted : March 25, 2015
Last Update Posted : March 5, 2019
Sponsor:
Collaborator:
The TIMI Study Group
Information provided by (Responsible Party):
Daiichi Sankyo, Inc.

Tracking Information
First Submitted Date  ICMJE October 28, 2008
First Posted Date  ICMJE October 29, 2008
Results First Submitted Date  ICMJE February 5, 2015
Results First Posted Date  ICMJE March 25, 2015
Last Update Posted Date March 5, 2019
Study Start Date  ICMJE November 2008
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 12, 2015)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 28, 2008)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 12, 2015)
  • 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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 28, 2008)
  • To compare DU-176b to warfarin with regard to the composite clinical outcome of stroke, SEE, and all-cause mortality [ Time Frame: 24 Months ]
  • To compare DU-176b to warfarin with regard to major bleeding events [ Time Frame: 24 Months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Global Study to Assess the Safety and Effectiveness of Edoxaban (DU-176b) vs Standard Practice of Dosing With Warfarin in Patients With Atrial Fibrillation
Official Title  ICMJE 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)
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE
  • Stroke
  • Atrial Fibrillation
  • Embolism
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 24, 2014)
21105
Original Estimated Enrollment  ICMJE
 (submitted: October 28, 2008)
16500
Actual Study Completion Date  ICMJE May 2013
Actual Primary Completion Date April 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Bulgaria,   Canada,   Chile,   China,   Colombia,   Croatia,   Czechia,   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,   United States
Removed Location Countries Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT00781391
Other Study ID Numbers  ICMJE DU176b-C-U301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
URL: https://vivli.org/ourmember/daiichi-sankyo/
Responsible Party Daiichi Sankyo, Inc.
Study Sponsor  ICMJE Daiichi Sankyo, Inc.
Collaborators  ICMJE The TIMI Study Group
Investigators  ICMJE Not Provided
PRS Account Daiichi Sankyo, Inc.
Verification Date March 2015

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