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

NCT03284463 | Completed Phase 2

• 1 other identifier: NFEC-2017-130
• Study Type: interventional
• Target: 306
• Locations: 1 country
• Sites: 8

Brief 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.

Conditions

Acute Stroke

Keywords

acute ischemic stroke; glibenclamide; rt-PA; blood-brain barrier; brain edema

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Early improvement: The proportion of NIHSS decreased ≥ 4 points

  7 days after the stroke onset

• Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT

  96 hours after the stroke onset

• Midline shift: The proportion of midline shift ≥ 6 mm in cranial CT

  96 hours after the stroke onset

• Functional outcome 2: The modified Rankin Scale distribution

  90 days after the stroke onset

• Functional outcome 3: The proportion of Barthel Index of 60-100 points

  90 days after the stroke onset

Other Outcomes (6)

• Mortality

  90 days after the stroke onset

• Early neurological deterioration

  24 hours after the stroke onset

• Hypoglycemia

  5 days after the stroke onset

Study Arms (2)

Glibenclamide

ACTIVE COMPARATOR

Glibenclamide Tablets

Drug: Glibenclamide

Placebo

PLACEBO COMPARATOR

Placebo for Glibenclamide

Drug: Placebo

Interventions

Glibenclamide DRUG

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.

Glibenclamide

Placebo DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (8)

Huadu District People's Hospital of Guangzhou

Guangzhou, Guangdong, 510515, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

Heyuan People's Hospital

Heyuan, Guangdong, China

Location

Maoming People's Hospital

Maoming, Guangdong, China

Location

Maoming Traditional Chinese Medical Hospital

Maoming, Guangdong, China

Location

Hainan Provincial Hospital of Traditional Chinese Medicine

Haikou, Hainan, 570100, China

Location

Haikou People's Hospital

Haikou, Hainan, 570208, China

Location

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Jiangsu, 325000, China

Location

Related Publications (2)

• Huang K, Zhao X, Zhao Y, Yang G, Zhou S, Yang Z, Huang W, Weng G, Chen P, Duan C, Lin Z, Wang S, Liu X, Huang Y, Zhang J, Zhang X, Li H, Ye S, Gu Y, Zhu M, Chen W, Quan W, Liu N, Chen Q, Chang Y, He J, Ji Z, Wu Y, Pan S; SE-GRACE Collaborators. Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial. EClinicalMedicine. 2023 Nov 1;65:102305. doi: 10.1016/j.eclinm.2023.102305. eCollection 2023 Nov.

  PMID: 37965431 DERIVED

• Huang K, Ji Z, Wu Y, Huang Y, Li G, Zhou S, Yang Z, Huang W, Yang G, Weng G, Chen P, Pan S. Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial. BMC Neurol. 2020 Jun 11;20(1):239. doi: 10.1186/s12883-020-01823-z.

  PMID: 32527232 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Brain Edema

Interventions

Glyburide

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Study Officials

• Suyue Pan, M.D., Ph.D.

  Department of Neurology, Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2017
• First Posted: September 15, 2017
• Study Start: January 1, 2018
• Primary Completion: August 28, 2022
• Study Completion: May 28, 2023
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (8)