Efficacy of Butylphthalide on Symptomatic Atherosclerotic Stenosis in Middle Cerebral Artery

NCT06331494 | Not Yet Recruiting

• 1 other identifier: SICAS
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Ischemic Stroke, Acute; Intracranial Atherosclerosis

Keywords

dl-3-n-Butylphthalide; atherosclerotic stenosis; middle cerebral artery; stroke

Outcome Measures

Primary Outcomes (1)

• Changes in stenosis degree in the responsible artery

  Intracranial atherosclerosis is evaluated by high-resolution MRI vessel-wall imaging technique.

  180 days

Secondary Outcomes (7)

• Stroke recurrence

  180 days

• Change in plaque volumes the responsible artery

  90 days, 180 days

• Changes in hemorrhage and enhancement volumes of atherosclerotic plaque in the responsible artery

  90 days, 180 days

• Changes in National Institutes of Health Stroke Scale (NIHSS)

  10±3 days

• Proportion of patients with modified Rankin Scale score (mRS) 0-2

  90 days, 180 days

Study Arms (2)

Butylphthalide

EXPERIMENTAL

The Butylphthalide group will receive Butylphthalide Sodium Chloride injection (100ml, twice/day) for the initial 10±3 days, followed by oral Butylphthalide soft capsules (0.2g, triple/day) for day 11±3 to day 180.

Drug: Butylphthalide

Placebo

PLACEBO COMPARATOR

The Placebo group will receive Butylphthalide Placebo injection (100ml, twice/day) for the initial 10±3 days, followed by oral Butylphthalide Placebo soft capsules (0.2g, triple/day) for day 11±3 to day 180.

Drug: Placebo

Interventions

Butylphthalide DRUG

Butylphthalide Sodium Chloride injection for 10±3 days, oral Butylphthalide soft capsules for day 11±3 to day 180.

Also known as: DL-3-n-butylphthalide

Butylphthalide

Placebo DRUG

Butylphthalide Placebo injection for 10±3 days, oral Butylphthalide Placebo soft capsules for day 11±3 to day 180.

Also known as: Blank

Placebo

Eligibility Criteria

• Age: 55 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male aged 55-75 years;
• At least one of the following risk factors of atherosclerosis: hypertension, diabetes, hypercholesterolemia, or smoking;
• 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;
• NIHSS ≤ 20;
• mRS ≤ 2 at randomization (pre-morbid historical assessment);
• Participants understand the purpose of the study and have signed informed consent form.

You may not qualify if:

• Presence of intracranial hemorrhage or other pathological brain diseases;
• Plan to or have performed intravenous thrombolysis or mechanical thrombectomy therapy;
• Unable to undergo MRI examination;
• Use Butylphthalide during onset between randomization;
• Suspect of cardiac embolism, such as atrial fibrillation, artificial heart valves, endocarditis, etc;
• Contraindications for the use of clopidogrel or aspirin;
• Known allergy history of celery or butylphthalide;
• 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;
• History of intracranial hemorrhage, coagulation disorders, systemic bleeding, thrombocytopenia, or other hematological disorders;
• Plan to perform other surgical procedures or interventional treatments that may require termination of investigational drug use;
• Severe non-cerebrovascular diseases with an expected survival time less than 3 months;
• Actively participating in another drug or device trial;
• Use any drugs with the same or similar mechanism as Butylphthalide during the follow-up period;
• Unsuitable for this trial from the opinion of the investigators.

Sponsors & Collaborators

• First Affiliated Hospital, Sun Yat-Sen University: lead

Study Sites (1)

The First Affiliated Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

MeSH Terms

Conditions

Ischemic Stroke; Intracranial Arteriosclerosis; Stroke

Interventions

3-n-butylphthalide

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Intracranial Arterial Diseases; Arteriosclerosis; Arterial Occlusive Diseases

Study Officials

• Jinsheng Zeng

  First Affiliated Hospital, Sun Yat-Sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinsheng Zeng

CONTACT

+8613322800657; zengjs@pub.guangzhou.gd.cn

Shihui Xing

CONTACT

+8613602755395; xingshih@mail.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 11, 2024
• First Posted: March 26, 2024
• Study Start: March 15, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: March 26, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)