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

NCT ID: NCT03062319

Last Updated: 2024-12-27

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 321 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-06
• Study Completion Date: 2023-07-18

Brief Summary

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

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.

Conditions

Ischemic Stroke; Atrial Fibrillation; Atherothrombosis

Keywords

anticoagulant; antiplatelet

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Oral Anticoagulant

Intervention Type: DRUG

warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Antiplatelet Drug

Intervention Type: DRUG

aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol

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.

Group Type: ACTIVE_COMPARATOR

Oral Anticoagulant

Intervention Type: DRUG

warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Interventions

Oral Anticoagulant

warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban

Intervention Type: DRUG

Antiplatelet Drug

aspirin, clopidogrel, prasugrel, ticlopidine, or cilostazol

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Patients with an acute ischemic stroke or TIA from 8 days and up to 360 days from the onset of symptoms

2. Age 20 or older

3. Patients with non-valvular atrial fibrillation (chronic or paroxysmal) who start or continue taking an oral anticoagulant

4. Patients who have one of the following atherothrombotic diseases

1. A past history of ischemic heart disease (myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI)

2. A past history of peripheral artery disease (symptomatic peripheral arterial occlusive disease, lower extremity bypass surgery/angioplasty/stenting)

3. Carotid artery stenosis (symptomatic or asymptomatic (=>50% diameter), a history of carotid artery stenting (CAS) or carotid endarterectomy (CEA))

4. 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)

5. A past history of atherothrombotic brain infarction, lacunar infarction, or branch atheromatous disease

5. Patients without severe disability (modified Rankin Scale score =<4)

6. Patients who can take oral medications

7. Patients who can receive follow-up survey

8. Provision of written informed consent either directly or by a suitable surrogate

Exclusion Criteria

1. History of myocardial infarction or acute coronary syndrome within the past 12 months

2. Patients who underwent PCI with drug-eluting stents within the past 12 months or PCI with bare-metal stents within the past 3 months

3. Patients who underwent carotid artery stent placement, intracranial stent placement, or lower extremity stent placement within the past 3 months

4. History of symptomatic intracranial hemorrhage or gastrointestinal bleeding within the past 6 months

5. Hemorrhagic diathesis or blood coagulation disorders

6. Platelet counts <100,000 /mm3 at enrollment.

7. Severe anemia (hemoglobin <7 g/dL)

8. Severe renal failure (creatinine clearance =<15 mL/min) or undergoing chronic hemodialysis.

9. Severe liver dysfunction (Grade B or C of the Child-Pugh classification)

10. Patients with severe disability requires constant nursing care, bedridden (modified Rankin Scale score =5)

11. Pregnant or possibly pregnant women

12. Active cancer

13. Expectation of survival less than 2 years

14. Anticoagulant or antiplatelet is scheduled to be discontinued for more than 4 weeks during the follow-up period

15. Planned revascularization procedure during the follow-up period

16. Patients who are enrolled in other trials

17. Patients judged as inappropriate for this study by investigators

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Network for Clinical Stroke Trials

UNKNOWN

Sponsor Role: collaborator

The BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program

UNKNOWN

Sponsor Role: collaborator

National Hospital Organization Osaka National Hospital

OTHER

Sponsor Role: lead

Responsible Party

Hiroshi Yamagami

Director, Department of Stroke Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hiroshi Yamagami, MD

Role: PRINCIPAL_INVESTIGATOR

National Hospital Organization Osaka National Hospital

Locations

National Hospital Organization Osaka National Hospital

Osaka, Osaka, Japan

Countries

Japan

References

Okazaki S, Tanaka K, Yazawa Y, Doijiri R, Koga M, Ihara M, Yamamoto S, Kamiyama K, Honda Y, Uchida K, Yoshimoto T, Asakura K, Omae K, Tanaka K, Maeda H, Yamamoto H, Hirano T, Toyoda K, Iguchi Y, Noguchi T, Okada Y, Kitagawa K, Sakai N, Yamagami H; ATIS-NVAF Trial Investigators. Optimal Antithrombotics for Ischemic Stroke and Concurrent Atrial Fibrillation and Atherosclerosis: A Randomized Clinical Trial. JAMA Neurol. 2025 Oct 6. doi: 10.1001/jamaneurol.2025.3662. Online ahead of print.

Reference Type: DERIVED

PMID: 41051787 (View on PubMed)

Okazaki S, Yamamoto H, Asakura K, Omae K, Maeda H, Tanaka K, Yamamoto S, Hirano T, Iguchi Y, Sakaguchi M, Koga M, Ihara M, Toyoda K, Noguchi T, Sakai N, Yamagami H. Optimal antithrombotic therapy in ischemic stroke patients with non-valvular atrial fibrillation and atherothrombosis: study protocol for a randomized controlled trial. Front Neurol. 2024 Oct 23;15:1468523. doi: 10.3389/fneur.2024.1468523. eCollection 2024.

Reference Type: DERIVED

PMID: 39539664 (View on PubMed)

Other Identifiers

ATIS-NVAF

Identifier Type: -

Identifier Source: org_study_id