Optimal Antithrombotic Therapy in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation and Atherothrombosis

Study Overview
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Brief Summary
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The Purpose of this open-label randomized controlled multicenter trial is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis.

Detailed Description
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The Purpose of this open-label randomized controlled multicenter trial is to evaluate the efficacy and safety of mono-drug therapy with oral anticoagulant compared to combination therapy with antiplatelet drug, in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis. Target sample size is 400. The primary outcome is a composite endpoint of ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization) and major bleeding defined by the International Society on Thrombosis and Haemostasis(ISTH) criteria within 2 years after randomization.

Official Title
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Optimal Antithrombotic Therapy in Ischemic Stroke Patients With Non-Valvular Atrial Fibrillation and Atherothrombosis

Conditions
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Ischemic Stroke, Atrial Fibrillation, Atherothrombosis

Intervention / Treatment
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* Drug: Oral Anticoagulant
* Drug: Antiplatelet Drug


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with an acute ischemic stroke or TIA from 8 days and up to 360 days from the onset of symptoms Age 20 or older Patients with non-valvular atrial fibrillation (chronic or paroxysmal) who start or continue taking an oral anticoagulant Patients who have one of the following atherothrombotic diseases A past history of ischemic heart disease (myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) A past history of peripheral artery disease (symptomatic peripheral arterial occlusive disease, lower extremity bypass surgery/angioplasty/stenting) Carotid artery stenosis (symptomatic or asymptomatic (=>50% diameter), a history of carotid artery stenting (CAS) or carotid endarterectomy (CEA)) Intracranial artery stenosis (=>50% stenosis of the diameter of a major intracranial artery: intracranial internal carotid artery, anterior cerebral artery (ACA)-A1 and A2, middle cerebral artery (MCA)-M1 and M2, posterior cerebral artery (PCA)-P1 and P2, vertebral artery, and basilar artery; a history of intracranial stent placement or intracranial bypass surgery) A past history of atherothrombotic brain infarction, lacunar infarction, or branch atheromatous disease Patients without severe disability (modified Rankin Scale score =<4) Patients who can take oral medications Patients who can receive follow-up survey Provision of written informed consent either directly or by a suitable surrogate Exclusion Criteria: History of myocardial infarction or acute coronary syndrome within the past 12 months Patients who underwent PCI with drug-eluting stents within the past 12 months or PCI with bare-metal stents within the past 3 months Patients who underwent carotid artery stent placement, intracranial stent placement, or lower extremity stent placement within the past 3 months History of symptomatic intracranial hemorrhage or gastrointestinal bleeding within the past 6 months Hemorrhagic diathesis or blood coagulation disorders Platelet counts <100,000 /mm3 at enrollment. Severe anemia (hemoglobin <7 g/dL) Severe renal failure (creatinine clearance =<15 mL/min) or undergoing chronic hemodialysis. Severe liver dysfunction (Grade B or C of the Child-Pugh classification) Patients with severe disability requires constant nursing care, bedridden (modified Rankin Scale score =5) Pregnant or possibly pregnant women Active cancer Expectation of survival less than 2 years Anticoagulant or antiplatelet is scheduled to be discontinued for more than 4 weeks during the follow-up period Planned revascularization procedure during the follow-up period Patients who are enrolled in other trials Patients judged as inappropriate for this study by investigators

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Dual-therapy group<br>Dual-therapy group: single anticoagulant drug and single antiplatelet drug. The dosage is determined according to each drug's package insert in Japan. In patients treated with warfarin, the target international normalized ratio (INR) range of 2.0-3.0 for those <70 years and 1.6-2.6 for those =>70 years is recommended according to the Japanese guidelines. | Drug: Oral Anticoagulant<br>* warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban<br>Drug: Antiplatelet Drug<br>* aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol<br>|
| Active Comparator: Single-therapy group<br>Single-therapy group: single anticoagulant drug. The dosage is determined according to each drug's package insert in Japan. In patients treated with warfarin, the target international normalized ratio (INR) range of 2.0-3.0 for those <70 years and 1.6-2.6 for those =>70 years is recommended according to the Japanese guidelines. | Drug: Oral Anticoagulant<br>* warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite endpoint of ischemic cardiovascular events and major bleeding | One of the following ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, or ischemic events requiring urgent revascularization), or major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria | 2 years after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality | All-cause mortality | 2 years after randomization | 
| Ischemic cardiovascular events | Ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization) | 2 years after randomization | 
| All ischemic cardiovascular events including transient ischemia | All ischemic cardiovascular events including transient ischemia (cardiovascular death, ischemic stroke, transient ischemic attack (TIA), myocardial infarction, unstable angina pectoris, systemic embolism, progression of symptomatic peripheral artery disease, ischemic events requiring urgent revascularization) | 2 years after randomization | 
| Ischemic stroke | Ischemic stroke | 2 years after randomization | 
| Myocardial infarction and cardiovascular death | Myocardial infarction and cardiovascular death | 2 years after randomization | 
| major bleeding | major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria | 2 years after randomization | 
| Intracranial hemorrhage | Intracranial hemorrhage | 2 years after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulant, antiplatelet