Clinical trial NCT03718559: Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atrial Fibrillation
Coronary Artery Disease
Stable Angina
Stable Chronic Angina
Keywords: Edoxaban
antiplatelet
anticoagulant
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: CardioVascular Research Foundation, Korea
First posted: 2018-10-24
Enrollment: 1040
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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

Primary outcomes:
measure: Rate of net Clinical Outcome
timeFrame: 1 year
Secondary outcomes:
measure: Rate of all cause death
timeFrame: 1 year
measure: Rate of cardiovascular death
timeFrame: 1 year
measure: Rate of myocardial infarction
timeFrame: 1 year
measure: Rate of ischemic stroke
timeFrame: 1 year
measure: Rate of systemic embolism
timeFrame: 1 year
measure: Rate of unplanned revascularization
timeFrame: 1 year
measure: Rate of composite of hard outcomes
timeFrame: 1 year
measure: Rate of stent thrombosis
timeFrame: 1 year
measure: Rate of composite of Major or clinically relevant non-major bleeding
timeFrame: 1 year
measure: Rate of fatal bleeding
timeFrame: 1 year
measure: Rate of major bleeding
timeFrame: 1 year
measure: Rate of minor bleeding
timeFrame: 1 year
measure: Rate of intracranial hemorrhage
timeFrame: 1 year
measure: Rate of gastrointestinal hemorrhage
timeFrame: 1 year
Other outcomes:
Locations:
city: Anyang
country: Korea, Republic of
facility: Hallym University Medical Center
city: Bucheon
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Ilsan
country: Korea, Republic of
facility: Dongguk University Ilsan Hospital
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Pusan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Kangdong KyungHee University hospital
city: Seoul
country: Korea, Republic of
facility: Konkuk University Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic Univ. of Korea, Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: The Catholic Univ.of Korea Eunpyeong St.Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: VHS medical center
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St. Vincent's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan Univeristy Hospital
city: Yangsan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
Study officials:
affiliation: Department of Medicine, Asan Medical Center, University of Ulsan College of Medicine
name: Duk-woo Park, MD
role: PRINCIPAL_INVESTIGATOR
References: