Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease

Coronary Artery Disease Clinical Trial

— EPIC-CAD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03718559
• Other study ID #: AMCCVEP2018-01
• Status: Completed
• Phase: Phase 4
• Start date: May 14, 2019
• Est. completion date: November 8, 2023

Study information

• Verified date: March 2024
• Source: Asan Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1040
• Est. completion date: November 8, 2023
• Est. primary completion date: November 8, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

Inclusion Criteria

1. A subject was = 19 years of age

2. Patients with nonvalvular atrial fibrillation with high embolic risk (CHA2DS2-VASc score =2)

3. Patients with Stable coronary artery disease

• In cases where clinically significant moderate or more stenosis is present, but the percentage of stenosis is not specified on result of Coronary Angiogram (CAG) or Coronary computed tomography angiography (CCTA), the determination will be at the investigator's discretion.
• 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 or haemorrhage on Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) imaging test

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. Arteriovenous malformation vii. Vascular aneurysms viii. Spinal cord vascular abnormalities or intracerebral vascular abnormalities ix. Active bleeding x. Hemoglobin level <7.0 g/dL or platelet count = 50,000 / mm3 xi. 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

Related Conditions & MeSH terms

• Angina Pectoris
• Angina, Stable
• Atrial Fibrillation
• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia
• Stable Angina
• Stable Chronic Angina

Intervention

Drug:
• Edoxaban
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.
• Single Antiplatelet Agents
Type of antiplatelet agent is dependant upon the investigator's discretion, but aspirin 100mg once daily or clopidogrel 75mg once daily was recommended.

Locations

Country	Name	City	State
Korea, Republic of	Hallym University Medical Center	Anyang
Korea, Republic of	Soon Chun Hyang University Hospital Bucheon	Bucheon
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Dongguk University Ilsan Hospital	Ilsan
Korea, Republic of	Dong-A University Hospital	Pusan
Korea, Republic of	Inje University Haeundae Paik Hospital	Pusan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Kangdong KyungHee University hospital	Seoul
Korea, Republic of	Konkuk University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National 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	Seoul
Korea, Republic of	The Catholic University of Korea, St. Vincent's Hospital	Suwon
Korea, Republic of	Ulsan Univeristy Hospital	Ulsan
Korea, Republic of	Pusan National University Yangsan Hospital	Yangsan

Sponsors (2)

Lead Sponsor	Collaborator
Gi-Byoung Nam	CardioVascular Research Foundation, Korea

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Rate of all cause death		1 year
Secondary	Rate of cardiovascular death		1 year
Secondary	Rate of myocardial infarction		1 year
Secondary	Rate of ischemic stroke		1 year
Secondary	Rate of systemic embolism		1 year
Secondary	Rate of unplanned revascularization		1 year
Secondary	Rate of composite of hard outcomes	all cause death, myocardial infarction, ischemic stroke, and systemic embolism	1 year
Secondary	Rate of stent thrombosis		1 year
Secondary	Rate of composite of Major or clinically relevant non-major bleeding	Major bleeding; Fatal bleeding; Bleeding 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
Secondary	Rate of fatal bleeding	International Society on Thrombosis and Haemostasis(ISTH), The Bleeding Academic Research Consortium (BARC)5	1 year
Secondary	Rate of major bleeding	ISTH, BARC 3, The Thrombolysis in Myocardial Infarction (TIMI) major bleeding	1 year
Secondary	Rate of minor bleeding	ISTH, BARC and TIMI criteria	1 year
Secondary	Rate of intracranial hemorrhage		1 year
Secondary	Rate of gastrointestinal hemorrhage		1 year