- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04205578
NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events (NICE-MMD)
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Li Ma, MD, PhD
- Phone Number: 86-010-59978317
- Email: marygl@hotmail.com
Study Contact Backup
- Name: Zongze Li, MD
- Phone Number: 86-13121226581
- Email: lizongze@pkuih.edu.cn
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 102206
- Peking University International Hospital
-
Contact:
- Zongze Li, MD
- Phone Number: 86-13121226581
- Email: lizongze@pkuih.edu.cn
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Beijing, Beijing, China, 100079
- Beijing Tiantan Hospital, Capital Medical University
-
Contact:
- Li Ma, MD, PhD
- Phone Number: 86-010-59978317
- Email: marygl@hotmail.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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 3.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 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.
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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.
|
Placebo Comparator: 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.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Perioperative ischemic stroke rate
Time Frame: 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.
|
within 30 days after surgery
|
Perioperative death rate
Time Frame: within 30 days after surgery
|
Rate of perioperative death of any cause within 30 days after surgery
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within 30 days after surgery
|
Rate of transient neurological deficit (TND)
Time Frame: 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
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within 30 days after surgery
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
modified Rankin Scale scores at 30 days after surgery
Time Frame: at 30 days after surgery
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The modified Rankin Scale scores were recorded at 1 month after surgery.
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at 30 days after surgery
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The severity of transient neurological deficit
Time Frame: within 30 days after surgery
|
The severity of TND was further categorized into four grades based on the clinical symptoms and duration6: Grade 0, none TND; Grade 1, symptoms resolved within 5 days; Grade 2, symptoms prolonged for 5 to 9 days; Grade 3; symptoms prolonged for 10 or more days.
One grade worse was scored if there were hemiparesis and/or seizure.
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within 30 days after surgery
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Postoperative intracranial hemorrhagic event
Time Frame: within 30 days after surgery
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New-onset intracranial hemorrhage within 30 days after surgery and confirmed by CT or MRI.
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within 30 days after surgery
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Yuanli Zhao, MD, Beijing Tiantan Hospital
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Necrosis
- Cardiovascular Diseases
- Vascular Diseases
- Cerebrovascular Disorders
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Arterial Occlusive Diseases
- Brain Ischemia
- Carotid Artery Diseases
- Brain Infarction
- Cerebral Arterial Diseases
- Intracranial Arterial Diseases
- Infarction
- Stroke
- Ischemic Stroke
- Ischemia
- Ischemic Attack, Transient
- Cerebral Infarction
- Moyamoya Disease
- Physiological Effects of Drugs
- Platelet Aggregation Inhibitors
- Neuroprotective Agents
- Protective Agents
- 3-n-butylphthalide
Other Study ID Numbers
- KY2019-023
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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