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Completed

NCT Number: NCT00781391

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

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.

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Key information

Conditions

Stroke Arrhythmias, Cardiac Atrial Fibrillation Brain Diseases Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Embolism Embolism and Thrombosis Heart Diseases Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Vascular Diseases

Age range

21 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Bahía Blanca, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

warfarin tablets

Drug

Warfarin tablets plus Edoxaban placebo tablets each taken once daily for 24 months

Edoxaban tablets (high dose regimen-60mg)

Drug

Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months

Edoxaban tablets (low dose regimen-30mg)

Drug

Edoxaban tablets plus warfarin placebo tablets each taken once daily for 24 months

placebo warfarin

Drug

placebo warfarin

placebo edoxaban

Drug

placebo edoxaban

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Daiichi Sankyo

Industry

Collaborators

  • The TIMI Study Group

Registry information

Official study 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)

Acronym: EngageAFTIMI48

Important dates

Study start
2008
Primary completion
2013
Study completion
2013
First posted
Oct 29, 2008
Registry last updated
Mar 5, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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