Effectiveness of Butylphthalide on Dynamic Cerebral Autoregulation in Patients With Acute Ischemic Stroke. (EBCAS)

Effectiveness of Butylphthalide on Dynamic Cerebral Autoregulation in Patients With Large-artery Atherosclerosis Acute Ischemic Stroke(EBCAS)

This is a randomized, triple-blind, placebo-controlled, multicenter clinical trial. Eligible patients will be randomized into either the butylphthalide (NBP) or placebo group in a 2:1 ratio.The main purpose of this study is to determine whether butylphthalide can improve dynamic Cerebral Autoregulation (dCA) in large-artery atherosclerosis acute ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: butylphthalide(NBP); Drug: placebo

Detailed Description

Cerebral stroke, the first cause of death in China, seriously affects the health and living of people. Its high incidence, disability, mortality and recurrence rate give a heavy burden on the family, society and country. According to TOAST classification, large-artery atherosclerosis ischemic stroke is one of the most common subtypes, and majority experts demonstrate its dynamic Cerebral Autoregulation (dCA) is impaired in affected hemisphere.

Thrombolytic therapy with intravenous tissue plasminogen activator (tPA), which remains the only therapeutic drug for acute ischemic stroke approved by the US Food and Drug Administration, is limited by the narrow time window of thrombolysis, bleeding complications, or high costs. Other treatment strategies mainly utilize therapeutic agents to prevent or reduce cell damage from ischemia. Butylphthalide (NBP) is a multiple target drug for the treatment of acute mild to moderate ischemic cerebral stroke.

Cerebral autoregulation (CA) is the main mechanism that maintains relatively constant cerebral blood flow, which is critical for the normal functioning of physiological functions, as well as the occurrence, development and prognosis of the cerebral stroke.whether NBP can improve the dCA in large-artery atherosclerosis acute ischemic stroke has not been illustrated.

Thus, in this study, investigators plan to enroll 99 eligible patients, which will be randomized into either the NBP or placebo group in a 2:1 ratio within 90 days follow-up to explore whether NBP can improve the dCA in large-artery atherosclerosis acute ischemic stroke. DCA measurement will be performed at 0, 14 and 90 days after entering the trial, nurses will collect intravenous blood 6ml 3 times (each time before dCA measurement, the blood samples will be stored for laboratory test). Clinical information and follow-up information will be collected and recorded in case report form (CRF) once signing of informed consent.

• Study Type: Interventional
• Enrollment (Actual): 99
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130000
      • First hospital of Jilin University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ranging from 18 to 80, both genders;
• Within 48 hours symptoms onset;
• According to TOAST classification, diagnosed to be large-artery atherosclerosis ischemic stroke, without history of stroke in the past three months;
• 5≤National Institutes of Health Stroke Scale (NIHSS) ≤25;
• Unilateral internal carotid artery (ICA) or M1 segment of middle cerebral artery (MCA) stenosis (rate of stenosis ranging from 50-99%);
• Sufficient bilateral temporal bone windows for insonation of the middle cerebral artery;
• Glasgow Coma Scale (GCS) ≥ 8;
• Willing to participate and sign the informed consent.

Exclusion Criteria:

• Patients who have received or plan to undergo intravascular interventional treatment/thrombolytic therapy;
• Coma or agitation, and can't cooperate to complete dCA;
• Has been given butylphthalide injection or capsules;
• Arrhythmia, anemia and hyperthyroidism which may influence the stability of cerebral blood flow diagnosed by two physicians by electrocardiogram and laboratory tests;
• Other intracranial diseases, including cerebral hemorrhage (primary or secondary), intracranial neoplasm, aneurysm, arteriovenous malformation, etc;
• Alanine transaminase (ALT) or glutamic-oxalacetic transaminase (AST) continued to rise more than 3 times the upper limit of normal , creatinine clearance rate<30ml/min;
• Pre-stroke Modified Rankin Scale (mRS) score ≥ 2;
• Malignant neoplasm and expected lifetime < 2 years;
• Pregnant and lactating women;
• Participating in other trials or has been participated in other trials in recent 3 months;
• Dementia and mental illness.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: butylphthalide(NBP); Based on the standard medical care, 25mg of NBP injection, and 100ml of 0.9% saline; NBP capsule	Drug: butylphthalide(NBP); Standard medical care is in accordance with China Guideline for the diagnosis and treatment of acute ischemic stroke (2014), including medical care for vital signs, control of temperature, blood pressure and glucose, improving cerebral blood circulation, antiplatelet treatment and nutritional supportive care.In addition, 25mg butylphthalide(NBP) injection, and 100ml 0.9% saline by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, infusion for 14 days, then, butylphthalide(NBP) capsule for 76 days.
Placebo Comparator: placebo; Based on the standard medical care, 100ml of 0.9% saline as the placebo; starch capsule as the placebo	Drug: placebo; Standard medical care is in accordance with China Guideline for the diagnosis and treatment of acute ischemic stroke (2014), including medical care for vital signs, control of temperature, blood pressure and glucose, improving cerebral blood circulation, antiplatelet treatment and nutritional supportive care.In addition, 100ml 0.9% saline by an independent research nurse, sealed with brown bag in order to make the investigators and patients blinded, infusion for 14 days, then, starch capsule for 76 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase difference (PD) in degree	A dCA parameter derived from transfer function analysis.	within 14 days injection NBP,and 90 days of sequential therapy

Collaborators and Investigators

• Sponsor: Yi Yang

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2018
• Primary Completion (Actual): March 25, 2022
• Study Completion (Actual): May 25, 2022

Study Registration Dates

• First Submitted: January 18, 2018
• First Submitted That Met QC Criteria: January 26, 2018
• First Posted (Actual): January 29, 2018

Study Record Updates

• Last Update Posted (Actual): June 30, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: butylphthalide(NBP); large-artery atherosclerosis acute ischemic stroke; dynamic Cerebral Autoregulation(dCA)
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; 3-n-butylphthalide
• Other Study ID Numbers: EBCAS

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