safety and efficacy of glibenclamide combined with rt-pa in acute cerebral embolism

Conditions: Acute Stroke

Summary: 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)

Keywords: acute ischemic stroke glibenclamide rt-pa blood-brain barrier brain edema