Safety and Efficacy of Glibenclamide Combined With Rt-PA in Acute Cerebral Embolism

Acute Stroke Clinical Trial

— SE-GRACE  

Official title:

Safety and Efficacy of Glibenclamide Combined With Rt-PA in Treating Acute Ischemic Stroke: a Prospective, Randomized, Double-blind, Placebo-control, Multi-center Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03284463
• Other study ID #: NFEC-2017-130
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: January 1, 2018
• Est. completion date: May 28, 2023

Study information

• Verified date: June 2023
• Source: Nanfang Hospital of Southern Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is designed to evaluate the safety and efficacy of oral glibenclamide in acute ischemic stroke patients who under intravenous rt-PA thrombolysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 306
• Est. completion date: May 28, 2023
• Est. primary completion date: August 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA territory involvement in addition to primary MCA territory stroke is acceptable)
• Aged =18 and =74 years
• A baseline NIHSS score between 4 to 25
• Intravenous rt-PA thrombolysis conducted within 4.5 hours after stroke onset, if known, or the time last seen well [termed "time last known at neurologic baseline" (TLK@B)]
• The time to the start of administration of Study Drug must be =10 h after time of symptom onset or TLK@B
• Informed consent was signed by the subject or the legal representative

Exclusion Criteria:

• Prior to stroke, significant disability exists, with modified Rankin Scale >1 point
• With medical history or evidence of cerebral hemorrhage, subarachnoid hemorrhage, arteriovenous malformation, cerebral aneurysm or brain tumor
• With clinical or imaging evidence of contralateral cerebral infarction which is believed to have influence on the patient outcome by the investigators
• With clinical or imaging evidence of occlusion in vertebral or basilar artery
• With clinical evidence of brain herniation, e.g., one or two dilated, fixed pupils; unconsciousness (i.e., C2 on item 1a on the NIHSS); and/or loss of other brainstem reflexes, attributable to edema or herniation according to the investigator's judgment
• With gastrointestinal bleeding and instable hemodynamics or other causes that force the patient to stop nutritional support
• Renal disorder from the patient's history (e.g., dialysis) or eGFR of <60 mL/min/1.73 m2
• Severe liver disease, or ALT >3 times upper limit of normal or bilirubin >2 times normal (subjects may be randomized if liver function tests have been drawn but are not yet available and the subject has no known history of liver disease; however treatment with Study Drug cannot commence until liver function tests are available and indicate ALT >3 times upper limit of normal and bilirubin >2 times upper limit of normal)
• Blood glucose <3.0 mmol/L at enrollment or immediately prior to administration of Study Drug, or a clinically significant history of hypoglycemia
• Acute ST elevation myocardial infarction, and/or acute decompensated heart failure, and/or Tc > 520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an acute coronary syndrome, myocardial infarction, or coronary intervention within the past 3 months
• Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide/glibenclamide; glibenclamide plus metformin; Xiaoke Pill (a Chinese patent medicine with main effective constituent of glibenclamide); glimepiride; repaglinide; nateglinide; glipizide; gliclazide; tolbutamide; glibornuride
• Known treatment with bosentan within 7 days
• Known allergy to sulfa or specific allergy to sulfonylurea drugs
• Known G6PD enzyme deficiency
• Pregnant women. Women must be either postmenopausal (as confirmed by the LAR), permanently sterilized or, if =50 years old must have a negative test for pregnancy obtained before enrollment
• Breast-feeding women who do not agree (or their LAR does not agree) to stop breastfeeding during Study Drug infusion and for 7 days following the end of Study Drug infusion
• Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <6 months not related to current stroke, or those unlikely to be compliant with follow up
• Patients currently receiving an investigational drug
• Mentally incompetent (prior to qualifying stroke) patients and wards of the state
• Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented)

Related Conditions & MeSH terms

• Acute Stroke
• Stroke

Intervention

Drug:
• Glibenclamide
Glibenclamide is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days.
• Placebo
Placebo is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days.

Locations

Country	Name	City	State
China	Huadu District People's Hospital of Guangzhou	Guangzhou	Guangdong
China	Nanfang Hospital of Southern Medical University	Guangzhou	Guangdong
China	Haikou People's Hospital	Haikou	Hainan
China	Hainan Provincial Hospital of Traditional Chinese Medicine	Haikou	Hainan
China	Heyuan People's Hospital	Heyuan	Guangdong
China	Maoming People's Hospital	Maoming	Guangdong
China	Maoming Traditional Chinese Medical Hospital	Maoming	Guangdong
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Nanfang Hospital of Southern Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Mortality	The mortality at 90 days	90 days after the stroke onset
Other	Early neurological deterioration	The ratio of neurological deterioration (NIHSS increased = 4 points) within 24 hours after the onset	24 hours after the stroke onset
Other	Hypoglycemia	The incidence of hypoglycemia (random blood glucose < 3.9 mmol/L)	5 days after the stroke onset
Other	Cardiac events	The incidence of cardiac events in cardiac examination (ECG, echocardiography)	30 days after the stroke onset
Other	Pulmonary infection	The incidence of pulmonary infection	7 days within the stroke onset
Other	AEs and SAEs	The incidence of adverse event and serious adverse event	30 days after the stroke onset
Primary	Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points	The proportion of mordified Rankin Scale of 0 to 2 points at 90 days	90 days after the stroke onset
Secondary	Early improvement: The proportion of NIHSS decreased = 4 points	The proportion of NIHSS decreased = 4 points at 7 days	7 days after the stroke onset
Secondary	Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT	The proportion of parenchymal hemorrhagic transformation in cranial CT within 96 hours	96 hours after the stroke onset
Secondary	Midline shift: The proportion of midline shift = 6 mm in cranial CT	The proportion of midline shift = 6 mm in cranial CT within 96 hours	96 hours after the stroke onset
Secondary	Functional outcome 2: The modified Rankin Scale distribution	The modified Rankin Scale distribution at 90 days	90 days after the stroke onset
Secondary	Functional outcome 3: The proportion of Barthel Index of 60-100 points	The proportion of Barthel Index of 60-100 points	90 days after the stroke onset
Secondary	Functional outcome 4: The proportion of IQCODE of = 3.40	The proportion of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) of = 3.40 at 6 months and 1 year after the stroke onset	6 months and 1 year after the stroke onset
Secondary	Blood-brain barrier: The serum concentration of MMP-9	The serum concentration of MMP-9 at baseline, and at 24, 48, and 72 h	Baseline, 24, 48, and 72 hours after the stroke onset