Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease (EPIC-CAD)

A Multi-centre, Open-labelled, Randomized Controlled Trial Comparing Two Different Anticoagulation Strategies in High-risk Atrial Fibrillation and Stable Coronary Artery Disease

This study evaluates the efficacy and safety of Edoxaban with the combination of edoxaban and antiplatelet in patients with stable CAD (coronary artery stenosis ≥50% on medical treatment or revascularized stable CAD [≥ 12 months for acute coronary syndrome and ≥ 6 months after stable CAD]) and high-risk atrial fibrillation (CHA2DS2-VASc score ≥2).

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease; Atrial Fibrillation; Stable Angina; Stable Chronic Angina
• Intervention / Treatment: Drug: Edoxaban Monotherapy; Drug: Edoxaban plus Single Antiplatelet Agent

• Study Type: Interventional
• Enrollment (Actual): 1040
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Anyang, Korea, Republic of
    • Hallym University Medical Center
  • Bucheon, Korea, Republic of
    • Soon Chun Hyang University Hospital Bucheon
  • Daegu, Korea, Republic of
    • Keimyung University Dongsan Medical Center
  • Ilsan, Korea, Republic of
    • Dongguk University Ilsan Hospital
  • Pusan, Korea, Republic of
    • Dong-A University Hospital
  • Pusan, Korea, Republic of
    • Inje University Haeundae Paik Hospital
  • Seongnam, Korea, Republic of
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Konkuk University Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
  • Seoul, Korea, Republic of
    • Kangdong KyungHee University Hospital
  • Seoul, Korea, Republic of
    • The Catholic Univ. of Korea, Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of
    • The Catholic Univ.of Korea Eunpyeong St.Mary's Hospital
  • Seoul, Korea, Republic of
    • VHS Medical Center
  • Suwon, Korea, Republic of
    • The Catholic university of Korea, St. Vincent's Hospital
  • Ulsan, Korea, Republic of
    • Ulsan Univeristy Hospital
  • Yangsan, Korea, Republic of
    • Pusan National University Yangsan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. A subject was ≥ 18 years of age
2. Patients with nonvalvular atrial fibrillation with high embolic risk (CHA2DS2-VASc score ≥2)

3. Patients with Stable coronary artery disease

   • Anatomically confirmed coronary artery disease (with ≥50% stenosis of major epicardial coronary artery documented by cardiac catheterization or coronary computed tomographic angiography) on medical therapy alone.
   • Revascularized coronary artery disease (either Percutaneous Coronary Intervention or coronary bypass surgery) whom the last revascularization should be performed ≥12 months before study enrollment for the acute coronary syndrome and ≥6 months for stable angina pectoris.

Exclusion Criteria

1. Patients with thrombocytopenia
2. High risk of bleeding which prohibits the anticoagulant use. (baseline comorbidities, hyper or hypercoagulable state, increased prothrombin time or activated partial thromboplastin time)
3. Prior history of intracranial haemorrhage
4. Mechanical prosthetic valve or moderate to severe mitral stenosis

5. The risk of bleeding increased due to the following reasons;

   • i. history of gastrointestinal ulcers within 1 month
   • ii. Malignant tumor with high risk of bleeding
   • iii. Brain or spinal cord injury within 1 month
   • iv. History of intracranial or intracerebral hemorrhage within 12 months
   • v. Esophageal varices
   • vi. Spinal cord vascular abnormalities or intracerebral vascular abnormalities
   • vii. Active bleeding
   • viii. Hemoglobin level <7.0 g/dL or platelet count ≤ 50,000 / mm3
   • ix. History of major surgery within 1 month
6. Uncontrolled severe hypertension
7. Hemodynamically Unstable or pulmonary embolism requiring thrombolysis or pulmonary embolectomy
8. History of hypersensitivity to Edoxaban, aspirin, or clopidogrel
9. Genetic problem with galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
10. Planned Percutaneous Coronary Intervention or coronary bypass surgery was planned within 1 year after randomization
11. Liver cirrhosis or liver dysfunction (AST or ALT > x3 of normal range or coagulation abnormality)
12. Estimated CrCl by Cockcroft-Gault equation<15 mL/min
13. Life expectancy less than 12 months
14. The subject was unable to provide written informed consent or participate in long-term follow-up
15. Pregnant and/or lactating women
16. Patients who are actively participating in another drug or device investigational study, which have not completed the primary endpoint follow-up period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Edoxaban alone	Drug: Edoxaban Monotherapy; Taking edoxaban (Lixiana™, Daiichi-Sankyo Inc.) 60mg once daily. The dose of edoxaban will be reduced to 30mg once daily in patients with estimated creatinine clearance 15≤CrCL≤50mL/min by Cockcroft-Gault equation or weight is ≤60kg.; Other Names: Lixiana™
Active Comparator: Combination of edoxaban plus single antiplatelet	Drug: Edoxaban plus Single Antiplatelet Agent; Type of antiplatelet agent is dependant upon the investigator's discretion, but aspirin 100mg once daily or clopidogrel 75mg once daily was recommended.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of net Clinical Outcome	composites of death, stroke, systemic embolic event, myocardial infarction, unplanned revascularization of a major coronary artery, major bleeding, and clinically relevant non-major bleeding event	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of all cause death		1 year
Rate of cardiovascular death		1 year
Rate of myocardial infarction		1 year
Rate of ischemic stroke		1 year
Rate of systemic embolism		1 year
Rate of unplanned revascularization		1 year
Rate of composite of hard outcomes	all cause death, myocardial infarction, ischemic stroke, and systemic embolism	1 year
Rate of stent thrombosis		1 year
Rate of fatal bleeding	International Society on Thrombosis and Haemostasis(ISTH), The Bleeding Academic Research Consortium (BARC)5	1 year
Rate of major bleeding	ISTH, BARC 3, The Thrombolysis in Myocardial Infarction (TIMI) major bleeding	1 year
Rate of minor bleeding	ISTH, BARC and TIMI criteria	1 year
Rate of intracranial hemorrhage		1 year
Rate of gastrointestinal hemorrhage		1 year
Rate of composite of Major or clinically relevant non-major bleeding	Major bleedingFatal bleedingBleeding in the critical site (Intracranial, retroperitoneal, intraocular, intraspinal, intra-articular, pericardial, intramuscular with compartment syndrome)Bleeding causing a fall in haemoglobin level of 2g/dL or leading to transfusion of two or more units of whole blood or red cells.; Clinically relevant non-major bleeding defined as any sign or symptom of haemorrhage that does not fit the criteria for The International Society on Thrombosis and Haemostasis (ISTH) major bleeding but requiring medical intervention, leading to hospitalization, or prompting a medical evaluation. Specifically bleeding that meet one of following criteria.; bleeding that resulted in hospitalization; medical or surgical intervention for bleeding; an unscheduled clinic visit, or; a change in physician-directed antithrombotic therapy.	1 year

Collaborators and Investigators

• Sponsor: Gi-Byoung Nam
• Collaborators: CardioVascular Research Foundation, Korea
• Investigators: Principal Investigator: Duk-woo Park, MD, Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2019
• Primary Completion (Actual): November 8, 2023
• Study Completion (Actual): November 8, 2023

Study Registration Dates

• First Submitted: October 23, 2018
• First Submitted That Met QC Criteria: October 23, 2018
• First Posted (Actual): October 24, 2018

Study Record Updates

• Last Update Posted (Actual): June 10, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: anticoagulant; antiplatelet; Edoxaban
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Pain; Neurologic Manifestations; Arrhythmias, Cardiac; Chest Pain; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Atrial Fibrillation; Angina Pectoris; Angina, Stable; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban; Platelet Aggregation Inhibitors
• Other Study ID Numbers: AMCCVEP2018-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No