Back to resultsGlibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage (GATE-ICH)
Primary Purpose
Intracerebral Hemorrhage
Status
Completed
Phase
Not Applicable
Locations
China
Study Type
Interventional
Intervention
Glibenclamide Tablets
Standard management for ICH
Sponsored by
About this trial
This is an interventional treatment trial for Intracerebral Hemorrhage focused on measuring Intracerebral hemorrhage, Perihematomal edema, Disability, Clinical trial
Eligibility Criteria
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
Sites / Locations
- Ankang Central Hospital
- Hanzhong Central Hospital
- Xijing Hospital
- Tangdu Hospital
- Xianyang Central Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Glibenclamide group
Control group
Arm Description
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.
Giving standard management for ICH
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
The change in the volume of ICH from the initial to follow-up CT scans
The change in the volume of PHE from the initial to follow-up CT scans
The change in the volume of ICH from the initial to follow-up CT scans
The change in the volume of PHE from the initial to follow-up CT scans
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).
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.
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).
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.
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).
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.
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).
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03741530
Brief Title
Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage
Acronym
GATE-ICH
Official Title
Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage (GATE-ICH): a Multi-center Randomized, Controlled, Assessor-blinded Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2020
Overall Recruitment Status
Completed
Study Start Date
December 15, 2018 (Actual)
Primary Completion Date
September 23, 2020 (Actual)
Study Completion Date
September 23, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Xijing Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Intracerebral Hemorrhage
Keywords
Intracerebral hemorrhage, Perihematomal edema, Disability, Clinical trial
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
220 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Glibenclamide group
Arm Type
Experimental
Arm Description
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.
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
Giving standard management for ICH
Intervention Type
Drug
Intervention Name(s)
Glibenclamide Tablets
Intervention Description
Giving glibenclamide tablets, 1.25 mg 3 times daily, orally or through gastric tube, for 7 consecutive days after enrollment.
Intervention Type
Other
Intervention Name(s)
Standard management for ICH
Intervention Description
Usual care and drug in hospital
Primary Outcome Measure Information:
Title
The proportion of death or major disability
Description
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).
Time Frame
90 days after the onset
Secondary Outcome Measure Information:
Title
The change in the volume of ICH from the initial to follow-up CT scans
Time Frame
3 days after onset
Title
The change in the volume of PHE from the initial to follow-up CT scans
Time Frame
3 days after onset
Title
The change in the volume of ICH from the initial to follow-up CT scans
Time Frame
7 days after onset
Title
The change in the volume of PHE from the initial to follow-up CT scans
Time Frame
7 days after onset
Title
The proportion of death or major disability
Description
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).
Time Frame
3 days after onset
Title
National Institute of Health stroke scale
Description
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.
Time Frame
3 days after onset
Title
Glasgow Coma Scale
Description
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).
Time Frame
3 days after onset
Title
Barthel Index
Description
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.
Time Frame
3 days after onset
Title
The proportion of death or major disability
Description
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).
Time Frame
7 days after onset
Title
National Institute of Health stroke scale
Description
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.
Time Frame
7 days after onset
Title
Glasgow Coma Scale
Description
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).
Time Frame
7 days after onset
Title
Barthel Index
Description
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.
Time Frame
7 days after onset
Title
Barthel Index
Description
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.
Time Frame
90 days after onset
Other Pre-specified Outcome Measures:
Title
Incidence of hypoglycemia
Description
Blood glucose <3.1 mmol/L
Time Frame
7 days after admission
Title
Incidence of symptomatic hypoglycemia
Description
Blood glucose <3.1 mmol/L with investigator-identified hypoglycemic symptoms
Time Frame
7 days after admission
Title
Incidence of cardiac-related Adverse Events and Serious Adverse Events
Time Frame
7 days after admission
Title
Incidence of all-cause mortality
Time Frame
90 days after onset
Title
Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame
During hospitalization
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wen Jiang, PhD
Organizational Affiliation
Department of Neurology, Xijing Hospital, Fourth Military Medical
Official's Role
Study Director
Facility Information:
Facility Name
Ankang Central Hospital
City
Ankang
State/Province
Shaanxi
ZIP/Postal Code
725000
Country
China
Facility Name
Hanzhong Central Hospital
City
Hanzhong
State/Province
Shaanxi
ZIP/Postal Code
723000
Country
China
Facility Name
Xijing Hospital
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710032
Country
China
Facility Name
Tangdu Hospital
City
Xi'an
State/Province
Shaanxi
ZIP/Postal Code
710038
Country
China
Facility Name
Xianyang Central Hospital
City
Xianyang
State/Province
Shaanxi
ZIP/Postal Code
712000
Country
China
12. IPD Sharing Statement
Citations:
PubMed Identifier
22698888
Citation
Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012 Aug;11(8):720-31. doi: 10.1016/S1474-4422(12)70104-7. Epub 2012 Jun 13.
Results Reference
background
PubMed Identifier
12411653
Citation
Gebel JM Jr, Jauch EC, Brott TG, Khoury J, Sauerbeck L, Salisbury S, Spilker J, Tomsick TA, Duldner J, Broderick JP. Natural history of perihematomal edema in patients with hyperacute spontaneous intracerebral hemorrhage. Stroke. 2002 Nov;33(11):2631-5. doi: 10.1161/01.str.0000035284.12699.84.
Results Reference
background
PubMed Identifier
14753483
Citation
Inaji M, Tomita H, Tone O, Tamaki M, Suzuki R, Ohno K. Chronological changes of perihematomal edema of human intracerebral hematoma. Acta Neurochir Suppl. 2003;86:445-8. doi: 10.1007/978-3-7091-0651-8_91.
Results Reference
background
PubMed Identifier
15178826
Citation
Butcher KS, Baird T, MacGregor L, Desmond P, Tress B, Davis S. Perihematomal edema in primary intracerebral hemorrhage is plasma derived. Stroke. 2004 Aug;35(8):1879-85. doi: 10.1161/01.STR.0000131807.54742.1a. Epub 2004 Jun 3.
Results Reference
background
PubMed Identifier
16361023
Citation
Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006 Jan;5(1):53-63. doi: 10.1016/S1474-4422(05)70283-0.
Results Reference
background
PubMed Identifier
26757714
Citation
Shi Y, Leak RK, Keep RF, Chen J. Translational Stroke Research on Blood-Brain Barrier Damage: Challenges, Perspectives, and Goals. Transl Stroke Res. 2016 Apr;7(2):89-92. doi: 10.1007/s12975-016-0447-9. Epub 2016 Jan 13. No abstract available.
Results Reference
background
PubMed Identifier
27807801
Citation
Jiang B, Li L, Chen Q, Tao Y, Yang L, Zhang B, Zhang JH, Feng H, Chen Z, Tang J, Zhu G. Role of Glibenclamide in Brain Injury After Intracerebral Hemorrhage. Transl Stroke Res. 2017 Apr;8(2):183-193. doi: 10.1007/s12975-016-0506-2. Epub 2016 Nov 3.
Results Reference
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PubMed Identifier
36177443
Citation
Zhao J, Song C, Li D, Yang X, Yu L, Wang K, Wu J, Wang X, Li D, Zhang B, Li B, Guo J, Feng W, Fu F, Gu X, Qian J, Li J, Yuan X, Liu Q, Chen J, Wang X, Liu Y, Wei D, Wang L, Shang L, Yang F, Jiang W; GATE-ICH Study Group. Efficacy and safety of glibenclamide therapy after intracerebral haemorrhage (GATE-ICH): A multicentre, prospective, randomised, controlled, open-label, blinded-endpoint, phase 2 clinical trial. EClinicalMedicine. 2022 Sep 23;53:101666. doi: 10.1016/j.eclinm.2022.101666. eCollection 2022 Nov.
Results Reference
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PubMed Identifier
33986719
Citation
Zhao J, Yang F, Song C, Li L, Yang X, Wang X, Yu L, Guo J, Wang K, Fu F, Jiang W. Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage (GATE-ICH): Study Protocol for a Multicenter Randomized, Controlled, Assessor-Blinded Trial. Front Neurol. 2021 Apr 27;12:656520. doi: 10.3389/fneur.2021.656520. eCollection 2021.
Results Reference
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Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage
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