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

• Status: Recruiting
• Trial end date: 2021-09-30
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Nanfang Hospital of Southern Medical University
• Treatments: Glyburide

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)