Moyamoya DiseasePhase 3NICE-MMDNCT04205578
NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events
A Phase 3 study testing dl-3-n-butylphthalide (NBP) and Normal Saline 0.9% Infusion Solution in people with Moyamoya Disease and Ischemic Cerebral Infarction, run by yuanli Zhao at 2 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Moyamoya Disease, Ischemic Cerebral Infarction, Ischemic Stroke
- What is being tested?
- dl-3-n-butylphthalide (NBP) and Normal Saline 0.9% Infusion Solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 450 participants
- Where
- 2 sitesChina
- Study dates
- Jan 2020to 31 Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
2 sites in 1 country.
China2 sites
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, 100079
Li Ma, MD, PhD, 86-010-59978317, marygl@hotmail.com
Peking University International Hospital
Beijing, Beijing Municipality, 102206
Zongze Li, MD, 86-13121226581, lizongze@pkuih.edu.cn
About this study
Official title: 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
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.
Read the 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.
- Conditions
- Moyamoya Disease, Ischemic Cerebral Infarction, Ischemic Stroke, Ischemic Cerebrovascular Accident, Transient Ischemic Attack
- Being tested
- dl-3-n-butylphthalide (NBP), Normal Saline 0.9% Infusion Solution
- Keywords
- Dl-3-n-butylphthalide, Revascularization surgery, Extracranial-to-intracranial revascularization, Direct bypass surgery, Combined bypass surgery, Indirect bypass surgery
- Medical subject headings
- Moyamoya Disease, Ischemic Stroke, Ischemic Attack, Transient
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dl-3-n-butylphthalide (NBP)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 0.9% Infusion SolutionDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Butylphthalide (NBP) | Active comparator | 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. Receives: Drug: dl-3-n-butylphthalide (NBP) |
| Normal saline | Placebo comparator | 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. Receives: Drug: Normal Saline 0.9% Infusion Solution |
What is being measured
The primary outcome is the main question the study is designed to answer.
Perioperative ischemic stroke rate
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.
Measured: within 30 days after surgery
Perioperative death rate
Rate of perioperative death of any cause within 30 days after surgery
Measured: within 30 days after surgery
Rate of transient neurological deficit (TND)
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
Measured: within 30 days after surgery
Secondary outcomes (3)
modified Rankin Scale scores at 30 days after surgery
The modified Rankin Scale scores were recorded at 1 month after surgery.
Measured: at 30 days after surgery
The severity of transient neurological deficit
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.
Measured: within 30 days after surgery
Postoperative intracranial hemorrhagic event
New-onset intracranial hemorrhage within 30 days after surgery and confirmed by CT or MRI.
Measured: within 30 days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2019
- Study startJan 2020 (estimated)
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Moyamoya DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 450 participants (estimated)
Sponsor and investigators
- Lead sponsor
- yuanli Zhao
- Sponsor type
- University, hospital or other
- Collaborators
- Peking University International Hospital
- Responsible party
- Sponsor-investigator, yuanli Zhao, Beijing Tiantan Hospital
- Investigators
- Yuanli Zhao, MD, Study director, Beijing Tiantan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04205578
- Sponsor's protocol ID
- KY2019-023
- Acronym
- NICE-MMD
- Status last verified
- Dec 2019
- First submitted
- 18 Dec 2019
- Last updated
- 19 Dec 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Study Protocol to be published in peer-reviewed journal
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04205578
- Acronym / sponsor ID
- NICE-MMD / KY2019-023
- Conditions
- Moyamoya Disease, Ischemic Cerebral Infarction, Ischemic Stroke, Ischemic Cerebrovascular Accident, Transient Ischemic Attack
- Keywords
- Dl-3-n-butylphthalide, Revascularization surgery, Extracranial-to-intracranial revascularization, Direct bypass surgery, Combined bypass surgery, Indirect bypass surgery
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 450 participants (estimated)
- Lead sponsor
- yuanli ZhaoUniversity, hospital or other
- Collaborators
- Peking University International Hospital
- Study start
- Jan 2020 (estimated)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 19 Dec 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Butylphthalide (NBP) | Active comparator | Drug: dl-3-n-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. |
| Normal saline | Placebo comparator | Drug: Normal Saline 0.9% Infusion SolutionFor 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Butylphthalide (NBP) |
| Normal Saline 0.9% Infusion Solution100 mL of normal saline was administered intravenously since the day of extracranial-to-intracranial bypass surgery and continued twice daily for 14 postoperative days. | Drug | Normal saline |
Primary outcome
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.
Perioperative death rate
Time frame: within 30 days after surgery
Rate of perioperative death of any cause 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
3 secondary outcomes
modified Rankin Scale scores at 30 days after surgery
Time frame: at 30 days after surgery
The severity of transient neurological deficit
Time frame: within 30 days after surgery
Postoperative intracranial hemorrhagic event
Time frame: within 30 days after surgery
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2019.
- Individual participant dataSharing planned: Yes. Study Protocol to be published in peer-reviewed journal
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuanli Zhao, MD study director
Beijing Tiantan Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing dl-3-n-butylphthalide (NBP) and Normal Saline 0.9% Infusion Solution in people with Moyamoya Disease and Ischemic Cerebral Infarction, run by yuanli Zhao at 2 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zongze Li, MD (86-13121226581, lizongze@pkuih.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Perioperative ischemic stroke rate (time frame: within 30 days after surgery). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2019.