Acute Stroke
Conditions
Keywords
acute ischemic stroke, glibenclamide, rt-PA, blood-brain barrier, brain edema
Brief 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.
Interventions
DRUGGlibenclamide
Glibenclamide is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days.
DRUGPlacebo
Placebo is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days.
Sponsors
Nanfang Hospital, Southern Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 74 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points | 90 days after the stroke onset | The proportion of mordified Rankin Scale of 0 to 2 points at 90 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT | 96 hours after the stroke onset | The proportion of parenchymal hemorrhagic transformation in cranial CT within 96 hours |
| Early improvement: The proportion of NIHSS decreased ≥ 4 points | 7 days after the stroke onset | The proportion of NIHSS decreased ≥ 4 points at 7 days |
| Midline shift: The proportion of midline shift ≥ 6 mm in cranial CT | 96 hours after the stroke onset | The proportion of midline shift ≥ 6 mm in cranial CT within 96 hours |
| Functional outcome 2: The modified Rankin Scale distribution | 90 days after the stroke onset | The modified Rankin Scale distribution at 90 days |
| Functional outcome 3: The proportion of Barthel Index of 60-100 points | 90 days after the stroke onset | The proportion of Barthel Index of 60-100 points |
| Functional outcome 4: The proportion of IQCODE of ≤ 3.40 | 6 months and 1 year after the stroke onset | The proportion of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) of ≤ 3.40 at 6 months and 1 year after the stroke onset |
| Blood-brain barrier: The serum concentration of MMP-9 | Baseline, 24, 48, and 72 hours after the stroke onset | The serum concentration of MMP-9 at baseline, and at 24, 48, and 72 h |
Other
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemia | 5 days after the stroke onset | The incidence of hypoglycemia (random blood glucose \< 3.9 mmol/L) |
| Cardiac events | 30 days after the stroke onset | The incidence of cardiac events in cardiac examination (ECG, echocardiography) |
| Pulmonary infection | 7 days within the stroke onset | The incidence of pulmonary infection |
| AEs and SAEs | 30 days after the stroke onset | The incidence of adverse event and serious adverse event |
| Early neurological deterioration | 24 hours after the stroke onset | The ratio of neurological deterioration (NIHSS increased ≥ 4 points) within 24 hours after the onset |
| Mortality | 90 days after the stroke onset | The mortality at 90 days |
Countries
China
Outcome results
None listed