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Trial record 1 of 1 for:    ENGAGE AF-TIMI 48
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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.

Study Description
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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.

Condition or disease Intervention/treatment 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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 21105 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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)
Study Start Date : November 2008
Actual Primary Completion Date : April 2013
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.



Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00781391


Locations
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Sponsors and Collaborators
Daiichi Sankyo, Inc.
The TIMI Study Group
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Daiichi Sankyo, Inc.
ClinicalTrials.gov Identifier: NCT00781391    
Other Study ID Numbers: DU176b-C-U301
First Posted: October 29, 2008    Key Record Dates
Results First Posted: March 25, 2015
Last Update Posted: March 5, 2019
Last Verified: March 2015
Individual Participant Data (IPD) Sharing Statement:
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
Statistical Analysis Plan (SAP)
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/
Keywords provided by Daiichi Sankyo, Inc.:
Systemic embolic events
Additional relevant MeSH terms:
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Atrial Fibrillation
Embolism
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Embolism and Thrombosis
Vascular Diseases
Warfarin
 Edoxaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action