Ischemic Stroke, Acute Clinical Trial
— SICASOfficial title:
Efficacy of Butylphthalide on Symptomatic Atherosclerotic Stenosis in Middle Cerebral Artery (SICAS): a Prospective, Randomized, Double-blinded, Placebo-controlled, Multiple-center Trial.
Ischemic stroke with high incidence, mortality, disability and recurrence rate, has become the leading threat to the health worldwide. Intracranial atherosclerotic stenosis (ICAS) is commonly associated with ischemic stroke, especially in Chinese residents. Patients with severe ICAS are subject to a very high risk of recurrent stroke events, despite best medical therapy available. Unstable or complex atherosclerotic plaques can lead to plaque ruptures and distal embolisms, thereby increasing the risk of ischemic stroke recurrence. Studies have shown that activation of inflammatory states may play a driving role in the formation and development of atherosclerosis. So far, it remains unclear which are the best treatments for this condition, especially for high-risk patients. Dl-3-n-butylphthalide (NBP) is a Class I novel drug independently developed in China and was officially approved for use in acute ischemic stroke. Preclinical data showed that NBP can act multiple effects of anti-inflammation, antioxidation and anti-apoptosis by suppressing pro-inflammatory factors and upregulating the expression of anti-inflammatory factors. It is still undetermined whether combined therapy with NBP could enhance the curative effect of intracranial atherosclerosis. The primary purpose of this trial is to evaluate the efficacy of butylphthalide in reducing the degree of arterial stenosis and stabilizing plaques in patients with severe symptomatic middle cerebral artery stenosis.
| Status | Not yet recruiting |
| Enrollment | 140 |
| Est. completion date | August 31, 2026 |
| Est. primary completion date | May 31, 2026 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 55 Years to 75 Years |
| Eligibility | Inclusion Criteria: 1. Female or male aged 55-75 years; 2. At least one of the following risk factors of atherosclerosis: hypertension, diabetes, hypercholesterolemia, or smoking; 3. Symptomatic atherosclerotic stenosis in middle cerebral artery: large artery atherosclerotic cerebral infarction or TIA within 7 days of onset; 70%-99% stenosis of the responsible middle cerebral artery [M1] confirmed by high-resolution MRI examination (referred to Warfarin-Aspirin Symptomatic Intracranial Disease standard); new-onset infarction confirmed by diffusion weighted imaging (DWI) or TIA symptoms in the territory of the responsible artery supply; 4. NIHSS = 20; 5. mRS = 2 at randomization (pre-morbid historical assessment); 6. Participants understand the purpose of the study and have signed informed consent form. Exclusion Criteria: 1. Presence of intracranial hemorrhage or other pathological brain diseases; 2. Plan to or have performed intravenous thrombolysis or mechanical thrombectomy therapy; 3. Unable to undergo MRI examination; 4. Use Butylphthalide during onset between randomization; 5. Suspect of cardiac embolism, such as atrial fibrillation, artificial heart valves, endocarditis, etc; 6. Contraindications for the use of clopidogrel or aspirin; 7. Known allergy history of celery or butylphthalide; 8. Severe liver dysfunction (aspartate aminotransferase or alanine transaminase > 2 times normal upper limit) or severe renal dysfunction (creatinine value > 1.5 times normal upper limit), heart failure, asthma, etc; 9. History of intracranial hemorrhage, coagulation disorders, systemic bleeding, thrombocytopenia, or other hematological disorders; 10. Plan to perform other surgical procedures or interventional treatments that may require termination of investigational drug use; 11. Severe non-cerebrovascular diseases with an expected survival time less than 3 months; 12. Actively participating in another drug or device trial; 13. Use any drugs with the same or similar mechanism as Butylphthalide during the follow-up period; 14. Unsuitable for this trial from the opinion of the investigators. |
| Country | Name | City | State |
|---|---|---|---|
| China | The First Affiliated Hospital, Sun Yat-sen University | Guangzhou | Guangdong |
| Lead Sponsor | Collaborator |
|---|---|
| First Affiliated Hospital, Sun Yat-Sen University |
China,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Changes in stenosis degree in the responsible artery | Intracranial atherosclerosis is evaluated by high-resolution MRI vessel-wall imaging technique. | 180 days | |
| Secondary | Stroke recurrence | Rate of new-onset ischemic stroke or TIA in the territory of the symptomatic middle cerebral artery within 180 days. | 180 days | |
| Secondary | Change in plaque volumes the responsible artery | Change in plaque volumes in the symptomatic middle cerebral artery at 90 days and 180 days. | 90 days, 180 days | |
| Secondary | Changes in hemorrhage and enhancement volumes of atherosclerotic plaque in the responsible artery | Changes in hemorrhage and enhancement volumes of atherosclerotic plaque in the symptomatic middle cerebral artery at 90 days and 180 days. | 90 days, 180 days | |
| Secondary | Changes in National Institutes of Health Stroke Scale (NIHSS) | National Institutes of Health Stroke Scale (NIHSS, range: 0 - 42) at baseline and discharge. | 10±3 days | |
| Secondary | Proportion of patients with modified Rankin Scale score (mRS) 0-2 | Proportion of patients with modified Rankin Scale score (mRS) 0-2 at 90 days and 180 days. | 90 days, 180 days | |
| Secondary | Change in the value of cerebral blood flow (CBF) in the responsible artery territory | Qualitative analysis of regional cerebral blood flow (CBF) in arterial spin labeling sequence in the territory of the symptomatic middle cerebral artery at baseline, 90 days and 180 days. | 90 days, 180 days | |
| Secondary | Change in concentrations of serum lipid profiles | Concentrations of total cholesterol, serum triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol at baseline, discharge, 90 days and 180 days. | 10±3 days, 90 days, 180 days |