NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events
NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events
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.
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.
Inclusion Criteria:

 1. Males or females aged ≥ 18 and ≤ 60 years.

 2. 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.

 3. A clinical diagnosis of moyamoya disease, including unilateral and bilateral disease.

 4. Previous clinical diagnosis of stroke or transient ischemic attack or undiagnosed
 infarction evidenced on screening CT or MRI

 5. Patients with moyamoya disease underwent extra cranial-to-intracranial (EC-IC) bypass
 surgery, including direct or indirect or combined EC-IC bypass surgery

 6. 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.

 7. Ability to comply with study follow-up.

 Exclusion Criteria:

 1. Female subjects who are pregnant, lactating/breast-feeding, or plan to become pregnant
 within the next 3 months.

 2. severely disabled, as defined by a Modified Rankin Scale (mRS) score more than 3.

 3. History of intracranial hemorrhage.

 4. Postoperative intracranial hemorrhage on CT scan at 4 hours after surgery.

 5. Dementia or other progressive neurological disease.

 6. Known life expectancy < 6 months (for any reason).

 7. Known allergy or hypersensitivity to celery.

 8. 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.

 9. Persons unable or unlikely to return for follow-up visits.

 10. Any other reasons that, in the opinion of the investigator, make the subject
 unsuitable for enrollment.