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

• ClinicalTrials.gov Identifier: NCT03413202
• Recruitment Status: Recruiting
• First Posted: January 29, 2018
• Last Update Posted: July 28, 2020
• Sponsor: Yi Yang
• Information provided by (Responsible Party): Yi Yang, The First Hospital of Jilin University

Study Description

Brief Summary:

This is a randomized, triple-blind, placebo-controlled, multicenter clinical trial. investigators plan to enroll 774 eligible patients, which 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.

Condition or disease	Intervention/treatment	Phase
Acute Ischemic Stroke	Drug: butylphthalide(NBP); Drug: placebo	Phase 4

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 774 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, 10-14 and 83-97 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). High resolution nuclear magnetic resonance will conduct twice (0, 83-97days after entering the trial). Clinical information, neuroimaging data, biochemical examinations and follow-up information will be collected and recorded in case report form (CRF) once signing of informed consent.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effectiveness of Butylphthalide on Dynamic Cerebral Autoregulation in Patients With Large-artery Atherosclerosis Acute Ischemic Stroke(EBCAS)
• Actual Study Start Date: February 28, 2018
• Estimated Primary Completion Date: November 25, 2020
• Estimated Study Completion Date: February 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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;
• 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 drugs which can promote cerebral collateral circulation; establishment;
• 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.

Contacts and Locations

Contacts

Contact: Yi Yang, MD, PhD; 0086-13756661217; doctor_yangyi@163.com

Contact: Zhenni Guo, MD; zhen1ni2@163.com

Locations

China, Jilin

First Hospital of Jilin University; Recruiting

Changchun, Jilin, China, 130000

Contact: Yi Yang, MD, PhD doctor_yangyi@163.com

Sponsors and Collaborators

Yi Yang

Investigators

• Study Chair: Yi Yang, MD, PhD; Neuroscience Center, Department of Neurology, The First Hospital of Jilin University

More Information

• Responsible Party: Yi Yang, Associated Dean of First Hospital of Jilin University, The First Hospital of Jilin University
• ClinicalTrials.gov Identifier: NCT03413202
• Other Study ID Numbers: EBCAS
• First Posted: January 29, 2018
• Last Update Posted: July 28, 2020
• Last Verified: July 2020

• 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

Keywords provided by Yi Yang, The First Hospital of Jilin University:

butylphthalide(NBP); large-artery atherosclerosis acute ischemic stroke; dynamic Cerebral Autoregulation(dCA)

Additional relevant MeSH terms:

Stroke; Cerebral Infarction; Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; 3-n-butylphthalide; Platelet Aggregation Inhibitors; Neuroprotective Agents; Protective Agents; Physiological Effects of Drugs