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NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events (NICE-MMD)

Primary Purpose

Moyamoya Disease, Ischemic Cerebral Infarction, Ischemic Stroke

Status

Unknown status

Phase

Phase 3

Locations

China

Study Type

Interventional

Intervention

dl-3-n-butylphthalide (NBP)

Normal Saline 0.9% Infusion Solution

About this trial

This is an interventional diagnostic trial for Moyamoya Disease focused on measuring Dl-3-n-butylphthalide, Revascularization surgery, Extracranial-to-intracranial revascularization, Direct bypass surgery, Combined bypass surgery, Indirect bypass surgery

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Beijing Tiantan Hospital, Capital Medical University
Peking University International Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Butylphthalide (NBP)

Normal saline

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Perioperative death rate

Rate of perioperative death of any cause 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

Secondary Outcome Measures

modified Rankin Scale scores at 30 days after surgery

The modified Rankin Scale scores were recorded at 1 month 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.

Postoperative intracranial hemorrhagic event

New-onset intracranial hemorrhage within 30 days after surgery and confirmed by CT or MRI.

Full Information

NCT ID

NCT04205578

First Posted

December 18, 2019

Last Updated

December 18, 2019

Sponsor

yuanli Zhao

Collaborators

Peking University International Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04205578

Brief Title

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

Acronym

NICE-MMD

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Unknown status

Study Start Date

January 2020 (Anticipated)

Primary Completion Date

December 31, 2022 (Anticipated)

Study Completion Date

December 31, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

yuanli Zhao

Collaborators

Peking University International Hospital

4. Oversight

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.

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Randomized

Enrollment

450 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Butylphthalide (NBP)

Arm Type

Active Comparator

Arm Description

Arm Title

Normal saline

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

dl-3-n-butylphthalide (NBP)

Intervention Description

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

Intervention Name(s)

Normal Saline 0.9% Infusion Solution

Intervention Description

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.

Primary Outcome Measure Information:

Title

Perioperative ischemic stroke rate

Description

Time Frame

within 30 days after surgery

Title

Perioperative death rate

Description

Rate of perioperative death of any cause within 30 days after surgery

Time Frame

within 30 days after surgery

Title

Rate of transient neurological deficit (TND)

Description

Time Frame

within 30 days after surgery

Secondary Outcome Measure Information:

Title

modified Rankin Scale scores at 30 days after surgery

Description

The modified Rankin Scale scores were recorded at 1 month after surgery.

Time Frame

at 30 days after surgery

Title

The severity of transient neurological deficit

Description

Time Frame

within 30 days after surgery

Title

Postoperative intracranial hemorrhagic event

Description

New-onset intracranial hemorrhage within 30 days after surgery and confirmed by CT or MRI.

Time Frame

within 30 days after surgery

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Zongze Li, MD

Phone

86-13121226581

lizongze@pkuih.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Li Ma, MD, PhD

Phone

86-010-59978317

marygl@hotmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Yuanli Zhao, MD

Organizational Affiliation

Beijing Tiantan Hospital

Official's Role

Study Director

Facility Information:

Facility Name

Beijing Tiantan Hospital, Capital Medical University

City

Beijing

State/Province

Beijing

ZIP/Postal Code

100079

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Li Ma, MD, PhD

Phone

86-010-59978317

marygl@hotmail.com

Facility Name

Peking University International Hospital

City

Beijing

State/Province

Beijing

ZIP/Postal Code

102206

Country

China

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Zongze Li, MD

Phone

86-13121226581

lizongze@pkuih.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Study Protocol to be published in peer-reviewed journal

IPD Sharing Time Frame

Since the publication of study protocol

IPD Sharing Access Criteria

Available from the principle investigator upon reasonable request

Learn more about this trial

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

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