Early Versus Late Initiation of Anticoagulation in Mild-to-moderate AIS Patients With NVAF

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the effectiveness between early and late initiation of anticoagulation therapy in acute ischemic stroke (AIS) patients with non-valvular atrial fibrillation (NVAF). Participants will be 1:1 randomized into early or late initiation group. The primary endpoint is early neurological deterioration (END) before discharge.

Detailed Description
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Anticoagulation therapy is effective to prevent ischemic stroke in patients with NVAF who have a history of stroke. Recent clinical trials have demonstrated that early initiation of anticoagulation therapy after AIS is safe, while no remarkable benefits have been observed. The goal of this clinical trial is to compare the effectiveness between early and late initiation of anticoagulation therapy in AIS patients with non-NVAF. Participants will be 1:1 randomized into early or late initiation group. The primary endpoint is END before discharge.

Official Title
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Early Versus Late Initiation of Anticoagulation in Mild-to-moderate Acute Ischemic Stroke Patients With Non-valvular Atrial Fibrillation

Conditions
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Acute Ischemic Stroke, Atrial Fibrillation

Intervention / Treatment
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* Drug: Anticoagulation Agents


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 years old Acute ischemic stroke with onset < 48 hours Have a history or newly diagnosed as NVAF NIHSS on admission <= 8 Exclusion Criteria: Chronic renal dysfunction (GFR < 30ml/min) or severe hepatic injury Have a history or newly diagnosed as valvular heart disease Mural thrombus in heart Contraindications of anticoagulation therapy within 12 days after AIS, e.g. severe intracranial hemorrhage Received reperfusion therapy, e.g. intravenous thrombolysis and endovascular treatment Concomitant stenosis (>50%) of carotid artery/intracranial artery, of which the ischemic lesion located within the territory Life expectancy less than 1 year Plan to receive invasive surgery in the following 3 months and have high risk of uncontrollable bleeding Pregnant or lactating women Individuals identified by researchers as unsuitable for participation in the study due to other reasons.

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early initiation of anticoagulation<br>For patients with NIHSS 0-3, anticoagulation therapy will be initiated within 0-3 days of onset. For patients with NIHSS 4-8, anticoagulation therapy will be initiated within 4-6 days of onset. | Drug: Anticoagulation Agents<br>* Anticoagulation agents includes rivaroxaban, dabigatran, apixaban, and edoxaban.<br>|
| Active Comparator: Late initiation of anticoagulation<br>For patients with NIHSS 0-3, anticoagulation therapy will be initiated within 4-12 days of onset. For patients with NIHSS 4-8, anticoagulation therapy will be initiated within 7-12 days of onset. | Drug: Anticoagulation Agents<br>* Anticoagulation agents includes rivaroxaban, dabigatran, apixaban, and edoxaban.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early neurological deterioration before discharge | NIHSS at discharge increase at least 2 points compared with NIHSS on admission | At discharge, an average of 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 90-day Composite events | Composite events including ischemic stroke, hemorrhagic stroke, myocardial infarction, systemic embolism, major extracranial hemorrhage, and vascular death within 90 days after enrollment | 90 days | 
| 90-day ischemic stroke | Ischemic stroke within 90 days after enrollment | 90 days | 
| 90-day hemorrhagic stroke | Hemorrhagic stroke within 90 days after enrollment | 90 days | 
| 90-day myocardial infarction | Myocardial infarction within 90 days after enrollment | 90 days | 
| 90-day systemic embolism | Systemic embolism within 90 days after enrollment | 90 days | 
| 90-day major extracranial hemorrhage | Major extracranial hemorrhage within 90 days after enrollment | 90 days | 
| 90-day non-major bleeding | Non-major bleeding within 90 days after enrollment | 90 days | 
| 90-day vascular death | Vascular death within 90 days after enrollment | 90 days | 
| 90-day all-cause death | All-cause death within 90 days after enrollment | 90 days | 
| Discharge mRS | Modified Rankin scale at discharge | At discharge, an average of 7 days |