Safety and Efficacy of Glibenclamide Combined With Rt-PA in Acute Cerebral Embolism (SE-GRACE)

Nanfang Hospital, Southern Medical University

Status and phase

Completed

Phase 3

Phase 2

Conditions

Acute Stroke

Treatments

Drug: Glibenclamide

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT03284463

NFEC-2017-130

Details and patient eligibility

About

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

Enrollment

306 patients

Sex

All

Ages

18 to 74 years old

Volunteers

No Healthy Volunteers

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)