NCT03741530

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
220

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Dec 2018

Typical duration for not_applicable

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 8, 2018

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 15, 2018

Completed
1 month until next milestone

Study Start

First participant enrolled

December 15, 2018

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 23, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 23, 2020

Completed
Last Updated

April 8, 2022

Status Verified

September 1, 2020

Enrollment Period

1.8 years

First QC Date

November 8, 2018

Last Update Submit

April 7, 2022

Conditions

Intracerebral Hemorrhage

Keywords

Intracerebral hemorrhagePerihematomal edemaDisabilityClinical trial

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (13)

  • 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

    3 days after onset

  • +8 more secondary outcomes

Other Outcomes (5)

  • Incidence of hypoglycemia

    7 days after admission

  • Incidence of symptomatic hypoglycemia

    7 days after admission

  • Incidence of cardiac-related Adverse Events and Serious Adverse Events

    7 days after admission

  • +2 more other outcomes

Study Arms (2)

Glibenclamide group

EXPERIMENTAL

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 TabletsOther: Standard management for ICH

Control group

PLACEBO COMPARATOR

Giving standard management for ICH

Other: Standard management for ICH

Interventions

Glibenclamide TabletsDRUG

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

Glibenclamide group
Standard management for ICHOTHER

Usual care and drug in hospital

Control groupGlibenclamide group

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Ankang Central Hospital

Ankang, Shaanxi, 725000, China

Location

Hanzhong Central Hospital

Hanzhong, Shaanxi, 723000, China

Location

Xijing Hospital

Xi'an, Shaanxi, 710032, China

Location

Tangdu Hospital

Xi'an, Shaanxi, 710038, China

Location

Xianyang Central Hospital

Xianyang, Shaanxi, 712000, China

Location

Related Publications (9)

  • 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.

    PMID: 22698888BACKGROUND

  • 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.

    PMID: 12411653BACKGROUND

  • 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.

    PMID: 14753483BACKGROUND

  • 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.

    PMID: 15178826BACKGROUND

  • 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.

    PMID: 16361023BACKGROUND

  • 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.

    PMID: 26757714BACKGROUND

  • 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.

    PMID: 27807801BACKGROUND

  • 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.

    PMID: 36177443DERIVED

  • 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.

    PMID: 33986719DERIVED

MeSH Terms

Conditions

Cerebral Hemorrhage

Interventions

Glyburide

Condition Hierarchy (Ancestors)

Intracranial HemorrhagesCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesHemorrhagePathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonylurea CompoundsUreaAmidesOrganic ChemicalsSulfonesSulfur Compounds

Study Officials

  • Wen Jiang, PhD

    Department of Neurology, Xijing Hospital, Fourth Military Medical

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 8, 2018

First Posted

November 15, 2018

Study Start

December 15, 2018

Primary Completion

September 23, 2020

Study Completion

September 23, 2020

Last Updated

April 8, 2022

Record last verified: 2020-09

Locations

CN(5)