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

December 18, 2019 updated by: yuanli Zhao

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.

Study Overview

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

Interventional

Enrollment (Anticipated)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Beijing
      • Beijing, Beijing, China, 102206
        • Peking University International Hospital
        • Contact:
      • Beijing, Beijing, China, 100079
        • Beijing Tiantan Hospital, Capital Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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.
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
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
within 30 days after surgery

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
The modified Rankin Scale scores were recorded at 1 month after surgery.
at 30 days after surgery
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.
within 30 days after surgery
Postoperative intracranial hemorrhagic event
Time Frame: within 30 days after surgery
New-onset intracranial hemorrhage within 30 days after surgery and confirmed by CT or MRI.
within 30 days after surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Investigators

  • Study Director: Yuanli Zhao, MD, Beijing Tiantan Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

January 1, 2020

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

December 18, 2019

First Submitted That Met QC Criteria

December 18, 2019

First Posted (Actual)

December 19, 2019

Study Record Updates

Last Update Posted (Actual)

December 19, 2019

Last Update Submitted That Met QC Criteria

December 18, 2019

Last Verified

December 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD 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

IPD Sharing Supporting Information Type

  • Study Protocol

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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