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

NCT04205578 | Unknown Phase 3 DMC

• 1 other identifier: KY2019-023
• Study Type: interventional
• Target: 450
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (3)

• 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.

  within 30 days after surgery

• Perioperative death rate

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

  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

  within 30 days after surgery

Secondary Outcomes (3)

• modified Rankin Scale scores at 30 days after surgery

  at 30 days after surgery

• The severity of transient neurological deficit

  within 30 days after surgery

• Postoperative intracranial hemorrhagic event

  within 30 days after surgery

Study Arms (2)

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.

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.

Drug: Normal Saline 0.9% Infusion Solution

Interventions

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.

Butylphthalide (NBP)

Normal Saline 0.9% Infusion Solution 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.

Normal saline

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• yuanli Zhao: lead
• Peking University International Hospital: collaborator

Study Sites (2)

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100079, China

Location

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

Location

MeSH Terms

Conditions

Moyamoya Disease; Ischemic Stroke; Ischemic Attack, Transient

Interventions

3-n-butylphthalide; Saline Solution

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Arterial Diseases; Intracranial Arterial Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Brain Ischemia

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Yuanli Zhao, MD

  Beijing Tiantan Hospital

  STUDY DIRECTOR

Central Study Contacts

Zongze Li, MD

CONTACT

86-13121226581; lizongze@pkuih.edu.cn

Li Ma, MD, PhD

CONTACT

86-010-59978317; marygl@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Department of Neurosurgery

Study Record Dates

• First Submitted: December 18, 2019
• First Posted: December 19, 2019
• Study Start: January 1, 2020
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: December 19, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Since the publication of study protocol
• Access Criteria: Available from the principle investigator upon reasonable request

Locations

CN (2)