NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events

NCT ID: NCT04205578

Last Updated: 2019-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

450 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-31

Study Completion Date

2022-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Moyamoya Disease Ischemic Cerebral Infarction Ischemic Stroke Ischemic Cerebrovascular Accident Transient Ischemic Attack

Keywords

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Direct bypass surgery Combined bypass surgery Indirect bypass surgery Dl-3-n-butylphthalide Revascularization surgery Extracranial-to-intracranial revascularization

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

dl-3-n-butylphthalide (NBP)

Intervention Type DRUG

25 mg of NBP in 100 mL of normal saline was administered intravenously since the day of extracranial-to-intracranial bypass surgery and continued twice daily for 14 postoperative days.

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.

Group Type PLACEBO_COMPARATOR

Normal Saline 0.9% Infusion Solution

Intervention Type DRUG

100 mL of normal saline was administered intravenously since the day of extracranial-to-intracranial bypass surgery and continued twice daily for 14 postoperative days.

Interventions

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dl-3-n-butylphthalide (NBP)

25 mg of NBP in 100 mL of normal saline was administered intravenously since the day of extracranial-to-intracranial bypass surgery and continued twice daily for 14 postoperative days.

Intervention Type DRUG

Normal Saline 0.9% Infusion Solution

100 mL of normal saline was administered intravenously since the day of extracranial-to-intracranial bypass surgery and continued twice daily for 14 postoperative days.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Peking University International Hospital

OTHER

Sponsor Role collaborator

yuanli Zhao

OTHER

Sponsor Role lead

Responsible Party

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yuanli Zhao

Professor, Department of Neurosurgery

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Yuanli Zhao, MD

Role: STUDY_DIRECTOR

Beijing Tiantan Hospital

Locations

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Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, China

Site Status

Peking University International Hospital

Beijing, Beijing Municipality, China

Site Status

Countries

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China

Central Contacts

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Zongze Li, MD

Role: CONTACT

Phone: 86-13121226581

Email: [email protected]

Li Ma, MD, PhD

Role: CONTACT

Phone: 86-010-59978317

Email: [email protected]

Facility Contacts

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Li Ma, MD, PhD

Role: primary

Zongze Li, MD

Role: primary

Other Identifiers

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KY2019-023

Identifier Type: -

Identifier Source: org_study_id