Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke

Study Overview
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Brief Summary
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The risk of early recurrence or progression of acute ischemic stroke is very high, even in patients treated with aspirin. The Chance study show that clopidogrel plus aspirin treatment reduced the risk of recurrent stroke in patients with transient ischemic attack (TIA) or minor ischemic stroke (NIHSS ≤ 3) within 24 hour onset and was not associated with increased hemorrhage events, compared with aspirin monotherapy. However, it is not known whether the dual antiplatelet treatment could reduce the risk of early recurrence or progression in patients with acute mild to moderate ischemic stroke (4 ≤ NIHSS ≤ 10). The investigators hypothesise that clopidogrel-aspirin treatment will be superior to aspirin monotherapy in this group of patients.

Detailed Description
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The ATAMIS study is a multicentre, prospective, randomised, open-label, controlled trial with a target enrollment of 3,000 patients from 60 centres of the Northeast China. Eligible patients are as follows: (1) definite acute ischemic stroke; (2) neurological deficit: 4 ≤ NIHSS ≤ 10; (3) time from onset to drug treatment: within 48 hours. Patients in the clopidogrel-aspirin group will receive a 300mg loading dose of clopidogrel, followed by clopidogrel 75 mg/d and aspirin 75 mg/d from day 2 to day 14, and followed by clopidogrel 75 mg/d or aspirin 100 mg/d from day 15 to day 90. Patients in the aspirin-alone group will receive 100-300 mg aspirin from day 1 to day 14, followed by aspirin 100 mg/d from day 15 to day 90. The primary efficacy end point is early neurological deterioration assessed as a change of NIHSS: no change of NIHSS within 14 days.

Official Title
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Antiplatelet Therapy in Acute Mild-Moderate Ischemic Stroke (ATAMIS): a Parallel Randomized, Open-label, Multicenter, Prospective Study

Conditions
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Ischemic Stroke

Intervention / Treatment
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* Drug: clopidogrel
* Drug: Aspirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Acute ischemic stroke that can be randomized within 48 hours of symptoms onset neurological deficit: 4 ≤ NIHSS ≤ 10 CT or MRI scan ruling out hemorrhage or other pathology the first onset of ischemic stroke or previous stroke with no obvious sequelae (mRS≤1) Signed informed consent by patient self or legally authorized representatives Exclusion Criteria: intracranial hemorrhage and hemorrhagic cerebral infarction Thrombolysis for ischemic stroke Allergy to clopidogrel and/or aspirin History of stroke with serious sequelae Severe systemic disease (such as severe infection, severe hepatic and renal dysfunction) Clear indication for anticoagulation (atrial fibrillation, mechanical cardiac valves, deep venous thrombosis, pulmonary embolism) History of intracranial hemorrhage Planned treatment with nonsteroidal anti-inflammatory drugs to affect platelet function Anticoagulation within 10 days Gastrointestinal bleed or major surgery within 3 months Planned or likely revascularization (any angioplasty or vascular surgery) within the next 3 months Planned surgery or intervention to stop antiplatelet therapy Ischemic stroke induced by angiography or surgery Pregnancy or childbirth within the previous 4 weeks Patients who have been treated with any other investigational drug within 3 months of enrollment Severe noncardiovascular comorbidity with life expectancy <3 months

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clopidogrel plus aspirin group<br>the group will receive a 300mg loading dose of clopidogrel plus aspirin 100 mg, followed by clopidogrel 75 mg/d and aspirin 100 mg/d from day 2 to day 14, and followed by clopidogrel 75 mg/d or aspirin 100 mg/d from day 15 to day 90. | Drug: clopidogrel<br> <br> * Other names: Plavix;Drug: Aspirin<br> <br> |
| Experimental: aspirin group<br>the group will receive 100-300 mg aspirin from day 1 to day 14, followed by aspirin 100 mg/d from day 15 to day 90. | Drug: Aspirin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early neurological deterioration assessed as change of NIHSS |  | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| new clinical vascular events (ischemic stroke/hemorrhagic stroke/TIA/myocardial infarction/vascular death) |  | 90 days | 
| Changes in National Institute of Health stroke scale scores |  | 14 days | 
| moderate to severe bleeding events | cerebral hemorrhage，hemorrhage of digestive tract, or moderate to severe bleeding of other organs. | 14 days | 
| Total mortality |  | 90 days | 
| Adverse events/severe adverse events |  | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, clopidogrel, antiplatelets