Tirofiban for the Prevention of Neurological Deterioration in Acute Ischemic Stroke

Study Overview
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Brief Summary
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Currently, dual antiplatelet therapy with aspirin and clopidogrel (with loading doses) is widely used for patients with acute ischemic stroke. However, immediate, potent and reversible inhibition of platelet aggregation is not possible. Additionally, more than 5% patients have aspirin resistance and more than 15% patients have clopidogrel resistance. Therefore, an intravenously administered GPIIb/IIIa receptor inhibitor (Tirofiban) receptor blocker with fast onset and offset of actions will provide more desired antiplatelet effects in the setting of acute ischemic stroke, especially in patients with high risk of neurological deterioration. This study will measure the anti-platelet effects of Tirofiban in patients with acute ischemic stroke who had high risk of neurological deterioration.

Official Title
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Safety and Efficacy of Tirofiban in Preventing Neurological Deterioration of Patients With Acute Ischemic Stroke: A Randomized Controlled Trial

Conditions
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Acute Stroke

Intervention / Treatment
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* Drug: Tirofiban Hydrochloride
* Drug: Oral antiplatelet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke with 24 hours of symptom onset. NIHSS≥4 and ≤20 points, and the paralyzed limbs is able to actively move the muscle (standardized motor examination rating scale of 2 or much higher). Age 18-80 years old. Informed consent obtained from patient or acceptable patient's surrogate. Exclusion Criteria: Treated with intravenous or endovascular thrombectomy for the indexed acute ischemic stroke. Acute ischemic stroke caused by determined or suspected cardioembolism. Acute ischemic stroke caused by other determined caused, including moyamoya disease, artery dissection, arteritis, and etc. Pre-stroke mRS ≥2 or the paralyzed limbs are dyskinesia before stroke. Known hematochezia, gastrointestinal bleeding and any other bleeding. Allergy to tirofiban or its solvents. Patients suffered from severe diseases, including malignant tumor, liver cirrhosis, kidney failure, congestive heart failure, and etc. Gastrointestinal or genitourinary tract bleeding within 1 years. Determined coagulation disorders, platelet dysfunction, or platelet count <100*109/L. Major surgical operation or severe trauma within 1 month. Hemorrhagic retinopathy. Chronic hemodialysis. Uncontrolled hypertension with systolic blood pressure >180 mmHg or diastolic blood pressure >110 mmHg. Acute pericarditis. Other conditions that determined by the investigators.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tirofiban+Oral antiplatelet therapy<br>Patients will receive Tirofiban in the first 72 hours and bridge to oral antiplatelet therapy thereafter. | Drug: Tirofiban Hydrochloride<br>* Tirofiban will use a loading dose, 0.4 μg/kg/min × 30 minutes, then 0.1μg/kg/min infusion for 71.5 hours.<br>Drug: Oral antiplatelet<br>* Aspirin, clopidogrel or other antiplatelet drugs. Loading dose will be considered if the patients is not on antiplatelet therapy.<br>|
| Active Comparator: Oral antiplatelet therapy<br>Patients will receive oral antiplatelet therapy alone. | Drug: Oral antiplatelet<br>* Aspirin, clopidogrel or other antiplatelet drugs. Loading dose will be considered if the patients is not on antiplatelet therapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with a change in NIHSS by ≥ 4 points compared to enrollment NIHSS. | National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms. | Within 72 hours of intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the NIHSS | National Health Institute Stroke Scale (NIHSS): stroke symptom severity scale with a range of 0-42. Higher score means more severe stroke symptoms. | 0-30 days of intervention. | 
| Change of the Scandinavian Stroke Scale | Scandinavian Stroke Scale (SSS): stroke symptom severity scale with a range of 0-58. Lower score means more severe stroke symptoms. | 0-30 days of intervention. | 
| The severity of global disability at 90 days, as assessed by modified Rankin scale (mRS). | The mRS is an ordinal, graded interval scale that assigns patients among 7 global disability levels, which ranging from 0 (no symptom) to 5 (severe disability) and 6 (death). | 0-90 days. | 
| Rate of symptomatic intracerebral hemorrhage. |  | 0-90 days | 
| Number of Participants experienced adverse events |  | 0-90 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute ischemic stroke, Neurological deterioration, Stroke progression