Clinical trial NCT03741530: Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage
Official title: Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage (GATE-ICH): a Multi-center Randomized, Controlled, Assessor-blinded Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Intracerebral Hemorrhage
Keywords: Intracerebral hemorrhage
Perihematomal edema
Disability
Clinical trial
Lead sponsor: Xijing Hospital
Sponsor class: OTHER
First posted: 2018-11-15
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Age 18-70 years with a primary ICH
2. A baseline CT with basal ganglia hemorrhage of 5 to 30 mL
3. Glasgow Coma Scale (GCS) score ≥ 6
4. Symptom onset less than 72 hours prior to admission
5. Informed consent

Exclusion Criteria:

1. Supratentorial ICH planned to evacuation of a large hematoma
2. Hemorrhage breaking into ventricles of brain
3. Prior significant disability (mRS ≥ 3)
4. Severe renal disease (i.e., renal disorder requiring dialysis ) or eGFR \<30ml/min/1.73m2
5. Severe liver disorder, or ALT \>3 times or bilirubin \>2 times upper limit of normal
6. Blood glucose \< 55 mg/dL (3.1 mmol/L）at enrollment, or with the history of hypoglycemia
7. 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
8. Treatment with sulfonylurea in the past 7 days, including glyburide, glyburide plus metformin, glimepiride, repaglinide, glipizide, gliclazide, tolbutamide and glibornuride
9. Treatment with bosentan in the past 7 days
10. Be allergic to sulfa or other sulfonylurea drugs
11. Known G6PD deficiency
12. Pregnant women
13. Breast-feeding women disagreeing to participate the study or stop breastfeeding during and after the study
14. Be enrolled in other non-observation-only study with receiving an investigational drug
15. Life expectancy \<3 months due to other diseases rather than current ICH
16. Refusing to be enrolled, or having poor compliance, or tending to withdraw

Primary outcomes:
measure: The proportion of death or major disability
timeFrame: 90 days after the onset
Secondary outcomes:
measure: The change in the volume of ICH from the initial to follow-up CT scans
timeFrame: 3 days after onset
measure: The change in the volume of PHE from the initial to follow-up CT scans
timeFrame: 3 days after onset
measure: The change in the volume of ICH from the initial to follow-up CT scans
timeFrame: 7 days after onset
measure: The change in the volume of PHE from the initial to follow-up CT scans
timeFrame: 7 days after onset
measure: The proportion of death or major disability
timeFrame: 3 days after onset
measure: National Institute of Health stroke scale
timeFrame: 3 days after onset
measure: Glasgow Coma Scale
timeFrame: 3 days after onset
measure: Barthel Index
timeFrame: 3 days after onset
measure: The proportion of death or major disability
timeFrame: 7 days after onset
measure: National Institute of Health stroke scale
timeFrame: 7 days after onset
measure: Glasgow Coma Scale
timeFrame: 7 days after onset
measure: Barthel Index
timeFrame: 7 days after onset
measure: Barthel Index
timeFrame: 90 days after onset
Other outcomes:
measure: Incidence of hypoglycemia
timeFrame: 7 days after admission
measure: Incidence of symptomatic hypoglycemia
timeFrame: 7 days after admission
measure: Incidence of cardiac-related Adverse Events and Serious Adverse Events
timeFrame: 7 days after admission
measure: Incidence of all-cause mortality
timeFrame: 90 days after onset
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: During hospitalization
Locations:
city: Ankang
country: China
facility: Ankang Central Hospital
state: Shaanxi
city: Hanzhong
country: China
facility: Hanzhong Central Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Xijing Hospital
state: Shaanxi
city: Xi'an
country: China
facility: Tangdu Hospital
state: Shaanxi
city: Xianyang
country: China
facility: Xianyang Central Hospital
state: Shaanxi
Study officials:
affiliation: Department of Neurology, Xijing Hospital, Fourth Military Medical
name: Wen Jiang, PhD
role: STUDY_DIRECTOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.