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

Sponsor

National Hospital Organization Osaka National Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT03062319

Collaborator

Network for Clinical Stroke Trials (Other), The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program (Other)

400

Enrollment

Locations

Arms

108.8

Anticipated Duration (Months)

200

Patients Per Site

1.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke Atrial Fibrillation Atherothrombosis	Drug: Oral Anticoagulant Drug: Antiplatelet Drug	Phase 4

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

400 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Apr 6, 2017

Anticipated Primary Completion Date :

Apr 30, 2022

Anticipated Study Completion Date :

Apr 30, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dual-therapy group 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 warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban Drug: Antiplatelet Drug aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol
Active Comparator: Single-therapy group 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 warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Arm

Intervention/Treatment

Active Comparator: Dual-therapy group

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

warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Drug: Antiplatelet Drug

aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol

Active Comparator: Single-therapy group

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

warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Outcome Measures

Primary Outcome Measures

Composite endpoint of ischemic cardiovascular events and major bleeding [2 years after randomization]
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

Secondary Outcome Measures

All-cause mortality [2 years after randomization]
All-cause mortality
Ischemic cardiovascular events [2 years after randomization]
Ischemic cardiovascular events (cardiovascular death, ischemic stroke, myocardial infarction, systemic embolism, ischemic events requiring urgent revascularization)
All ischemic cardiovascular events including transient ischemia [2 years after randomization]
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)
Ischemic stroke [2 years after randomization]
Ischemic stroke
Myocardial infarction and cardiovascular death [2 years after randomization]
Myocardial infarction and cardiovascular death
major bleeding [2 years after randomization]
major bleeding defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria
Intracranial hemorrhage [2 years after randomization]
Intracranial hemorrhage

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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