A Multi-center, Randomized, Single-blind, Placebo-controlled Study of Dl-3-n-butylphthalide in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events After Extracranial-to-intracranial Revascularization Surgery
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 450
- 试验地点
- 2
- 主要终点
- Rate of transient neurological deficit (TND)
研究概览
简要总结
An extracranial-to-intracranial (EC-IC) revascularization is the most widely used treatment to improve cerebral perfusion in patients with moyamoya disease (MMD), and it has been shown to reduce the risk of subsequent stroke and neurological deficit. However, perioperative changes in cerebral hemodynamics can induce fluctuations in cerebral perfusion that may lead to transient or irreversible neurological deficits. Our preliminary single-center study suggests that postoperative intravenous administration of dl-3-n-butylphthalide (NBP) may alleviate perioperative neurological deficits and improve the neurological outcomes after EC-IC revascularization for MMD. This is a multicenter, randomized, double-blind, single-controlled, add-on to standard of care study of NBP in patients with MMD of high risk for ischemic cerebrovascular events after EC-IC revascularization surgery.
详细描述
This trial is a prospective, randomized, singe-blinded, placebo parallel controlled, multiple-center trial.
A total of approximately 450 patients (age between18 years and 60 years) with moyamoya disease after EC-IC revascularization will be enrolled. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into two groups after offering informed content: 1) one group will receive butylphthalide in 100 mL of normal saline twice daily since the day of surgery and continued for 14 postoperative days; 2) the other group will receive 100 mL of normal saline twice daily since the day of surgery and continued for 14 postoperative days.
The primary objective is to evaluate the rate and severity of ischemic cerebral event in MMD patients with butylphthalide after EC-IC bypass surgery. The study consists of four visits including the day of randomization(baseline), postoperative day 1 before the first injection, 14 days after surgery when the injection therapy is done, and 30 after suryery. Demographic information, symptoms and signs, laboratory test, neuro-imaging assessment, neurological function scale will be recorded during the program. The rate of stroke event, neurological deficit and severity of neurological deficits will be assessed by modified Rankin scale. The trial is anticipated to last from January 2020 to December 2022 with subjects recruited form two neurosurgical centers in Beijing, China.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or females aged ≥ 18 and ≤ 60 years.
- •Women of childbearing potential (WOCBP) must have a negative urine HCG pregnancy test at Screening and be practicing a medically acceptable method of contraception with an annual failure rate of less than 1% until the completion of the trial or 60 days after discontinuation of study treatment. Women are considered not childbearing if they are > 1 year postmenopausal or surgically sterile (ie, hysterectomy, bilateral oophorectomy, or bilateral salpingectomy tubal ligation). If serum bHCG is the standard of care, then this value can be used to determine eligibility.
- •A clinical diagnosis of moyamoya disease, including unilateral and bilateral disease.
- •Previous clinical diagnosis of stroke or transient ischemic attack or undiagnosed infarction evidenced on screening CT or MRI
- •Patients with moyamoya disease underwent extra cranial-to-intracranial (EC-IC) bypass surgery, including direct or indirect or combined EC-IC bypass surgery
- •Capable of understanding the purpose and risk of the study and has signed, in writing, the ICF. If the subject is not capable of this at the time of enrollment, a legally authorized representative will provide written informed consent in accordance with all regulations.
- •Ability to comply with study follow-up.
排除标准
- •Female subjects who are pregnant, lactating/breast-feeding, or plan to become pregnant within the next 3 months.
- •severely disabled, as defined by a Modified Rankin Scale (mRS) score more than
- •History of intracranial hemorrhage.
- •Postoperative intracranial hemorrhage on CT scan at 4 hours after surgery.
- •Dementia or other progressive neurological disease.
- •Known life expectancy < 6 months (for any reason).
- •Known allergy or hypersensitivity to celery.
- •Received treatment with any other investigational drug within 30 days before baseline, was previously treated with NBP, is currently taking celery seed extract, or is currently participating in another clinical study.
- •Persons unable or unlikely to return for follow-up visits.
- •Any other reasons that, in the opinion of the investigator, make the subject unsuitable for enrollment.
研究组 & 干预措施
Butylphthalide (NBP)
For patients without obvious intracranial hemorrhage on CT scan at 4 hours after surgery, 25 mg of NBP in 100 mL of normal saline was administered intravenously since the day of surgery and continued twice daily for 14 postoperative days.
干预措施: dl-3-n-butylphthalide (NBP) (Drug)
Normal saline
For patients without obvious intracranial hemorrhage on CT scan at 4 hours after surgery, 100 mL of normal saline was administered intravenously since the day of surgery and continued twice daily for 14 postoperative days.
干预措施: Normal Saline 0.9% Infusion Solution (Drug)
结局指标
主要结局
Rate of transient neurological deficit (TND)
时间窗: within 30 days after surgery
TND was defined as either any reversible neurological deficits observed objectively (e.g., hemiparesis, dysarthria) or any reversible neurological deficits recognized and reported subjectively (e.g., facial palsy), and without evidence of intracranial hemorrhage and cerebral infarction on images
Perioperative ischemic stroke rate
时间窗: within 30 days after surgery
Perioperative cerebral stroke was defined as a symptomatic event of new cerebral infarction within 30 days after surgery and confirmed by CT or MRI. Symptoms included focal neurological deficit or headache lasting more than 24 hours.
Perioperative death rate
时间窗: within 30 days after surgery
Rate of perioperative death of any cause within 30 days after surgery
次要结局
- modified Rankin Scale scores at 30 days after surgery(at 30 days after surgery)
- The severity of transient neurological deficit(within 30 days after surgery)
- Postoperative intracranial hemorrhagic event(within 30 days after surgery)
研究者
yuanli Zhao
Professor, Department of Neurosurgery
Beijing Tiantan Hospital