Glibenclamide Advantage in Treating Edema After Intracerebral Hemorrhage

Intracerebral Hemorrhage Clinical Trial

— GATE-ICH  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03741530
• Other study ID #: KY20182067-X-3
• Status: Completed
• Phase: N/A
• Start date: December 15, 2018
• Est. completion date: September 23, 2020

Study information

• Verified date: September 2020
• Source: Xijing Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: September 23, 2020
• Est. primary completion date: September 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Hemorrhage
• Hemorrhage
• Intracerebral Hemorrhage

Intervention

Drug:
• Glibenclamide Tablets
Giving glibenclamide tablets, 1.25 mg 3 times daily, orally or through gastric tube, for 7 consecutive days after enrollment.

Other:
• Standard management for ICH
Usual care and drug in hospital

Locations

Country	Name	City	State
China	Ankang Central Hospital	Ankang	Shaanxi
China	Hanzhong Central Hospital	Hanzhong	Shaanxi
China	Tangdu Hospital	Xi'an	Shaanxi
China	Xijing Hospital	Xi'an	Shaanxi
China	Xianyang Central Hospital	Xianyang	Shaanxi

Sponsors (1)

Lead Sponsor	Collaborator
Xijing Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

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. Epub 2004 Jun 3. — View 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. — View 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. — View 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. — View 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. Review. — View 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. — View Citation

Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol. 2006 Jan;5(1):53-63. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of hypoglycemia	Blood glucose <3.1 mmol/L	7 days after admission
Other	Incidence of symptomatic hypoglycemia	Blood glucose <3.1 mmol/L with investigator-identified hypoglycemic symptoms	7 days after admission
Other	Incidence of cardiac-related Adverse Events and Serious Adverse Events		7 days after admission
Other	Incidence of all-cause mortality		90 days after onset
Other	Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)		During hospitalization
Primary	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	The change in the volume of ICH from the initial to follow-up CT scans		3 days after onset
Secondary	The change in the volume of PHE from the initial to follow-up CT scans		3 days after onset
Secondary	The change in the volume of ICH from the initial to follow-up CT scans		7 days after onset
Secondary	The change in the volume of PHE from the initial to follow-up CT scans		7 days after onset
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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