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