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

Phase 3

Completed

• Conditions: Stroke; Atrial Fibrillation; Embolism
• Interventions: Drug: Edoxaban tablets (low dose regimen-30mg); Drug: warfarin tablets; Drug: Edoxaban tablets (high dose regimen-60mg); Drug: placebo warfarin; Drug: placebo edoxaban

• Registration Number: NCT00781391
• Lead Sponsor: Daiichi Sankyo

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 available

Study Timeline

• Study First Submitted: 2008-10-28
• Study First Submitted QC: 2008-10-28
• Study First Posted: 2008-10-29
• Study Start: 2008-11
• Primary Completion: 2013-04
• Study Completion: 2013-05
• Results First Submitted: 2015-02-05
• Status Verified: 2015-03
• Results First Submitted QC: 2015-03-12
• Results First Posted: 2015-03-25
• Last Update Submitted: 2019-02-08
• Last Update Posted: 2019-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 21105

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
low dose edoxaban/placebo warfarin	Edoxaban tablets (low dose regimen-30mg)	Edoxaban tablets (30mg) plus warfarin placebo tablets
high dose edoxaban/placebo warfarin	placebo warfarin	Edoxaban tablets (60mg) plus warfarin placebo tablets
low dose edoxaban/placebo warfarin	placebo warfarin	Edoxaban tablets (30mg) plus warfarin placebo tablets
Warfarin/placebo edoxaban	warfarin tablets	Warfarin tablets plus placebo Edoxaban tablets
Warfarin/placebo edoxaban	placebo edoxaban	Warfarin tablets plus placebo Edoxaban tablets
high dose edoxaban/placebo warfarin	Edoxaban tablets (high dose regimen-60mg)	Edoxaban tablets (60mg) plus warfarin placebo tablets

Primary Outcome Measures

Name	Time	Method
Compare Edoxaban to Warfarin for Superiority for Composite of Stroke and Systemic Embolic Events (SEE).	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.
Compare Edoxaban to Warfarin for Composite of Stroke and Systemic Embolic Events (SEE).	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.

Secondary Outcome Measures

Name	Time	Method
Compare Edoxaban to Warfarin for Composite of Stroke, SEE, and All-cause Mortality	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	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.
Compare Edoxaban to Warfarin for Composite of Stroke, Systemic Embolic Event (SEE), and Cardiovascular (CV) Mortality	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	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.