Butyphthalide in Combination With Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke

Study Overview
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Brief Summary
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Acute ischemic stroke (AIS) is the most common type of stroke, which has high rate of morbidity, mortality and disability. A large number of studies have confirmed that the thrombolytic therapy can effectively open blood vessels and improve the functional prognosis of acute ischemic stroke. Therefore, all guidelines recommend giving thrombolysis treatment to acute ischemic stroke patients within 4.5 hours of onset. However, about 1/3 patients receiving thrombolysis will have good prognosis, while a large number of patients will still be disabled and even dead. How to improve the neurofunctional prognosis of thrombolytic patients has been a hot topic in the world. Butyl phthalide is type I chemical drugs. Some multicenter randomized, double-blind, placebo-controlled clinical trials have showed that acute ischemic stroke patients taking butyl phthalide has better lateral branch circulation and living ability score than patients taking placebo. Besides, butyl phthalide treatment is safe. The animal experiment indicated that buphthalein could significantly improve secondary side branch circulation, recover the microarterial diameter of the soft meninges in the ischemic region and increase the blood flow rate. Based on the discussion, we assume that: giving butyl phthalide to patients with acute ischemic stroke in advance, might promote and improve the formation of collateral circulation to freeze ischemia penumbra. Based on this hypothesis, we would like to explore the efficacy and safety of butyl phthalide combined with rtPA thrombolysis in the treatment of acute ischemic stroke.

Official Title
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Butyphthalide in Combination With Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke (BRAIS)：a Pilot, Prospective, Random, and Double Blinded Multi-center Study

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Drug: Butyphthalide combined with rtPA
* Drug: rtPA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >18 years; Diagnosis of anterior circulation infarct; First stroke onset or past stroke without obvious neurological deficit (mRS≤1); Time from onset to treatment ≤4.5 hours; SBP/DBP ≤ 180/110mmHg; No hemorrhagic imaging changes showed in CT; Signed informed consent by patient self or legally authorized representatives. Exclusion Criteria: History of stroke within 3 months; History of intracranial hemorrhage; Suspected subarachnoid hemorrhage; Intracranial tumour, vascular malformation or arterial aneurysm; Major surgery within 1 month; Systolic pressure ≥180 mmHg or diastolic pressure ≥110 mmHg; Platelet count < 100×109／L; Heparin therapy or oral anticoagulation therapy within 48 hours; Severe disease with a life expectancy of less than 3 months; Blood glucose < 50 mg/dL (2.7mmol/L); Patients who have received any other investigational drug or device within 3 months; Researchers consider patients inappropriate to participate in the registry. -

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rtPA combined with Butyphthalide<br>Intravenous treatment with 25mg butyphthalide, followed by intravenous throbolysis with 0.9mg/kg rtPA. Next day, intravenous treatment with 25mg butyphthalide 2 times/day for 14 days, followed by oral butyphthalide capsule (0.2g 3 times/day) to 90 days after thrombolysis. Other treatments were done according to guidelines. | Drug: Butyphthalide combined with rtPA<br>* Intravenous treatment with 25mg butyphthalide, followed by intravenous throbolysis with 0.9mg/kg rtPA. Next day, intravenous treatment with 25mg butyphthalide 2 times/day for 14 days, followed by oral butyphthalide capsule (0.2g 3 times/day) to 90 days after thrombolysis. Other treatments were done according to guidelines.<br>|
| Active Comparator: rtPA compared with placebo<br>Intravenous treatment with placebo injection, followed by intravenous throbolysis with 0.9mg/kg rtPA. Next day, intravenous treatment with placebo injection 2 times/day for 14 days, followed by oral placebo capsule (3 times/day) to 90 days after thrombolysis. Other treatments were done according to guidelines. | Drug: rtPA<br>* Intravenous thrombolysi with 0.9mg/kg rtPA, followed by other treatments according to guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of mRS score (0-2) (90 days) | Percentage of mRS score (0-2) at 90 days | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thrombolysis, Butyphthalide