Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage

Study Overview
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Brief Summary
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The purpose of the present study is to explore the efficacy of small doses of oral glibenclamide on brain edema after acute primary intracerebral hemorrhage (ICH), and improving the prognosis of patients.

Detailed Description
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In order to explore the efficacy and safety of oral glibenclamide on brain edema after acute primary ICH, a web-based 1:1 randomization process will be employed to assign 220 subjects to Glibenclamide group (giving standard management for ICH plus glibenclamide) or Control group (giving standard management for ICH). The investigators will make a neurofunctional assessment at baseline, and 3 days, 7 days, 90 days after enrollment. The investigators also assess the midline shift, and the change in the volume of ICH and perihematomal edema (PHE) from the initial to follow-up (3 days and 7days after enrollment). The serious adverse events of all-cause mortality, cardiac-related and blood glucose-related adverse events will be collected to assess the safety of glibenclamide.

Official Title
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Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage (GATE-ICH): a Multi-center Randomized, Controlled, Assessor-blinded Trial

Conditions
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Intracerebral Hemorrhage

Intervention / Treatment
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* Drug: Glibenclamide Tablets
* Other: Standard management for ICH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 years with a primary ICH A baseline CT with basal ganglia hemorrhage of 5 to 30 mL Glasgow Coma Scale (GCS) score ≥ 6 Symptom onset less than 72 hours prior to admission Informed consent Exclusion Criteria: Supratentorial ICH planned to evacuation of a large hematoma Hemorrhage breaking into ventricles of brain Prior significant disability (mRS ≥ 3) Severe renal disease (i.e., renal disorder requiring dialysis ) or eGFR <30ml/min/1.73m2 Severe liver disorder, or ALT >3 times or bilirubin >2 times upper limit of normal Blood glucose < 55 mg/dL (3.1 mmol/L）at enrollment, or with the history of hypoglycemia With acute ST elevation infarction, or decompensated heart failure, or cardiac arrest, or acute coronary syndrome, or known history of admission for acute coronary syndrome, or acute myocardial infarction, or coronary intervention in the past 3 months Treatment with sulfonylurea in the past 7 days, including glyburide, glyburide plus metformin, glimepiride, repaglinide, glipizide, gliclazide, tolbutamide and glibornuride Treatment with bosentan in the past 7 days Be allergic to sulfa or other sulfonylurea drugs Known G6PD deficiency Pregnant women Breast-feeding women disagreeing to participate the study or stop breastfeeding during and after the study Be enrolled in other non-observation-only study with receiving an investigational drug Life expectancy <3 months due to other diseases rather than current ICH Refusing to be enrolled, or having poor compliance, or tending to withdraw

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glibenclamide group<br>Giving standard management for ICH plus glibenclamide tablets, 1.25 mg 3 times daily, orally or through gastric tube, for 7 consecutive days after enrollment. | Drug: Glibenclamide Tablets<br>* Giving glibenclamide tablets, 1.25 mg 3 times daily, orally or through gastric tube, for 7 consecutive days after enrollment.<br>Other: Standard management for ICH<br>* Usual care and drug in hospital<br>|
| Placebo Comparator: Control group<br>Giving standard management for ICH | Other: Standard management for ICH<br>* Usual care and drug in hospital<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of death or major disability | Unfavourable outcome including death and disability is defined as patients achieving modified Rankin Scale (mRS) ≥3. The mRS is used for measuring the degree of disability or dependence in the daily activities of patients with stroke or other neurological diseases. The total score of the scale runs from 0 (perfect health without symptoms) to 6 (death). | 90 days after the onset | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change in the volume of ICH from the initial to follow-up CT scans |  | 3 days after onset | 
| The change in the volume of PHE from the initial to follow-up CT scans |  | 3 days after onset | 
| The change in the volume of ICH from the initial to follow-up CT scans |  | 7 days after onset | 
| The change in the volume of PHE from the initial to follow-up CT scans |  | 7 days after onset | 
| The proportion of death or major disability | Unfavourable outcome including death and disability is defined as patients achieving modified Rankin Scale (mRS) ≥3. The mRS is used for measuring the degree of disability or dependence in the daily activities of patients with stroke or other neurological diseases. The total score of the scale runs from 0 (perfect health without symptoms) to 6 (death). | 3 days after onset | 
| National Institute of Health stroke scale | The National Institutes of Health Stroke Scale (NIHSS) is used by healthcare providers to evaluate the impairment caused by stroke. The total score of the scale runs from 0 to 42. The higher score is an indicative of more severe impairment. | 3 days after onset | 
| Glasgow Coma Scale | The Glasgow Coma Scale is a scale for measuring the conscious state of patients with neurological diseases. The total score of the scale runs from 3 (deep coma or death) to 15 (fully awake person). | 3 days after onset | 
| Barthel Index | The Barthel Index scale is used to measure performance in activities of daily living (ADL). The total score of the scale runs from 0 to 100. The high score of the scale represents favourable performance in activities of daily life. | 3 days after onset | 
| The proportion of death or major disability | Unfavourable outcome including death and disability is defined as patients achieving modified Rankin Scale (mRS) ≥3. The mRS is used for measuring the degree of disability or dependence in the daily activities of patients with stroke or other neurological diseases. The total score of the scale runs from 0 (perfect health without symptoms) to 6 (death). | 7 days after onset | 
| National Institute of Health stroke scale | The National Institutes of Health Stroke Scale (NIHSS) is used by healthcare providers to evaluate the impairment caused by stroke. The total score of the scale runs from 0 to 42. The higher score is an indicative of more severe impairment. | 7 days after onset | 
| Glasgow Coma Scale | The Glasgow Coma Scale is a scale for measuring the conscious state of patients with neurological diseases. The total score of the scale runs from 3 (deep coma or death) to 15 (fully awake person). | 7 days after onset | 
| Barthel Index | The Barthel Index scale is used to measure performance in activities of daily living (ADL). The total score of the scale runs from 0 to 100. The high score of the scale represents favourable performance in activities of daily life. | 7 days after onset | 
| Barthel Index | The Barthel Index scale is used to measure performance in activities of daily living (ADL). The total score of the scale runs from 0 to 100. The high score of the scale represents favourable performance in activities of daily life. | 90 days after onset | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intracerebral hemorrhage, Perihematomal edema, Disability, Clinical trial