Safety and Efficacy of Glibenclamide Combined With Rt-PA in Acute Cerebral Embolism

This study is designed to evaluate the safety and efficacy of oral glibenclamide in acute ischemic stroke patients who under intravenous rt-PA thrombolysis.


Eligibility Criteria:
Inclusion Criteria:

* Clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA territory involvement in addition to primary MCA territory stroke is acceptable)
* Aged ≥18 and ≤74 years
* A baseline NIHSS score between 4 to 25
* Intravenous rt-PA thrombolysis conducted within 4.5 hours after stroke onset, if known, or the time last seen well \[termed "time last known at neurologic baseline" (TLK@B)\]
* The time to the start of administration of Study Drug must be ≤10 h after time of symptom onset or TLK@B
* Informed consent was signed by the subject or the legal representative

Exclusion Criteria:

* Prior to stroke, significant disability exists, with modified Rankin Scale \>1 point
* With medical history or evidence of cerebral hemorrhage, subarachnoid hemorrhage, arteriovenous malformation, cerebral aneurysm or brain tumor
* With clinical or imaging evidence of contralateral cerebral infarction which is believed to have influence on the patient outcome by the investigators
* With clinical or imaging evidence of occlusion in vertebral or basilar artery
* With clinical evidence of brain herniation, e.g., one or two dilated, fixed pupils; unconsciousness (i.e., C2 on item 1a on the NIHSS); and/or loss of other brainstem reflexes, attributable to edema or herniation according to the investigator's judgment
* With gastrointestinal bleeding and instable hemodynamics or other causes that force the patient to stop nutritional support
* Renal disorder from the patient's history (e.g., dialysis) or eGFR of \<60 mL/min/1.73 m2
* Severe liver disease, or ALT \>3 times upper limit of normal or bilirubin \>2 times normal (subjects may be randomized if liver function tests have been drawn but are not yet available and the subject has no known history of liver disease; however treatment with Study Drug cannot commence until liver function tests are available and indicate ALT \>3 times upper limit of normal and bilirubin \>2 times upper limit of normal)
* Blood glucose \<3.0 mmol/L at enrollment or immediately prior to administration of Study Drug, or a clinically significant history of hypoglycemia
* Acute ST elevation myocardial infarction, and/or acute decompensated heart failure, and/or Tc \> 520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an acute coronary syndrome, myocardial infarction, or coronary intervention within the past 3 months
* Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide/glibenclamide; glibenclamide plus metformin; Xiaoke Pill (a Chinese patent medicine with main effective constituent of glibenclamide); glimepiride; repaglinide; nateglinide; glipizide; gliclazide; tolbutamide; glibornuride
* Known treatment with bosentan within 7 days
* Known allergy to sulfa or specific allergy to sulfonylurea drugs
* Known G6PD enzyme deficiency
* Pregnant women. Women must be either postmenopausal (as confirmed by the LAR), permanently sterilized or, if ≤50 years old must have a negative test for pregnancy obtained before enrollment
* Breast-feeding women who do not agree (or their LAR does not agree) to stop breastfeeding during Study Drug infusion and for 7 days following the end of Study Drug infusion
* Patients already enrolled in a non-observation-only stroke study, or with life-expectancy \<6 months not related to current stroke, or those unlikely to be compliant with follow up
* Patients currently receiving an investigational drug
* Mentally incompetent (prior to qualifying stroke) patients and wards of the state
* Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented)