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Safety and Efficacy of Glibenclamide Combined With Rt-PA in Acute Cerebral Embolism (SE-GRACE)

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ClinicalTrials.gov Identifier: NCT03284463
Recruitment Status : Recruiting
First Posted : September 15, 2017
Last Update Posted : June 6, 2019
Sponsor:
Information provided by (Responsible Party):
Nanfang Hospital of Southern Medical University

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.

Condition or disease Intervention/treatment Phase
Acute Stroke Drug: Glibenclamide Drug: Placebo Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 306 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : September 30, 2020
Estimated Study Completion Date : September 30, 2021

Resource links provided by the National Library of Medicine

Drug Information available for: Glyburide

Arm Intervention/treatment
Active Comparator: Glibenclamide
Glibenclamide Tablets
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 Comparator: Placebo
Placebo for Glibenclamide
Drug: 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.




Primary Outcome Measures :
  1. Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points [ Time Frame: 90 days after the stroke onset ]
    The proportion of mordified Rankin Scale of 0 to 2 points at 90 days


Secondary Outcome Measures :
  1. Early improvement: The proportion of NIHSS decreased ≥ 4 points [ Time Frame: 7 days after the stroke onset ]
    The proportion of NIHSS decreased ≥ 4 points at 7 days

  2. Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT [ Time Frame: 96 hours after the stroke onset ]
    The proportion of parenchymal hemorrhagic transformation in cranial CT within 96 hours

  3. Midline shift: The proportion of midline shift ≥ 6 mm in cranial CT [ Time Frame: 96 hours after the stroke onset ]
    The proportion of midline shift ≥ 6 mm in cranial CT within 96 hours

  4. Functional outcome 2: The modified Rankin Scale distribution [ Time Frame: 90 days after the stroke onset ]
    The modified Rankin Scale distribution at 90 days

  5. Functional outcome 3: The proportion of Barthel Index of 60-100 points [ Time Frame: 90 days after the stroke onset ]
    The proportion of Barthel Index of 60-100 points

  6. Functional outcome 4: The proportion of IQCODE of ≤ 3.40 [ Time Frame: 6 months and 1 year after the stroke onset ]
    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

  7. Blood-brain barrier: The serum concentration of MMP-9 [ Time Frame: Baseline, 24, 48, and 72 hours after the stroke onset ]
    The serum concentration of MMP-9 at baseline, and at 24, 48, and 72 h


Other Outcome Measures:
  1. Mortality [ Time Frame: 90 days after the stroke onset ]
    The mortality at 90 days

  2. Early neurological deterioration [ Time Frame: 24 hours after the stroke onset ]
    The ratio of neurological deterioration (NIHSS increased ≥ 4 points) within 24 hours after the onset

  3. Hypoglycemia [ Time Frame: 5 days after the stroke onset ]
    The incidence of hypoglycemia (random blood glucose < 3.9 mmol/L)

  4. Cardiac events [ Time Frame: 30 days after the stroke onset ]
    The incidence of cardiac events in cardiac examination (ECG, echocardiography)

  5. Pulmonary infection [ Time Frame: 7 days within the stroke onset ]
    The incidence of pulmonary infection

  6. AEs and SAEs [ Time Frame: 30 days after the stroke onset ]
    The incidence of adverse event and serious adverse event



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03284463


Contacts
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Contact: Kaibin Huang, M.D., Ph.D. +8615915751065 hkb@smu.edu.cn

Locations
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China, Guangdong
Huadu District People's Hospital of Guangzhou Recruiting
Guangzhou, Guangdong, China, 510515
Contact: Guangning Li, M.D.       lgn621568@163.com   
Principal Investigator: Guangning Li, M.D.         
Nanfang Hospital of Southern Medical University Recruiting
Guangzhou, Guangdong, China
Contact: Kaibin Huang       hkb@smu.edu.cn   
Principal Investigator: Suyue Pan, M.D., Ph.D.         
Heyuan People's Hospital Recruiting
Heyuan, Guangdong, China
Contact: Yunqiang Huang, M.D.    +8613750225240    13750225240@126.com   
Principal Investigator: Yunqiang Huang, M.D.         
Maoming People's Hospital Recruiting
Maoming, Guangdong, China
Contact: Hao Li, M.D.       185416656@qq.com   
Principal Investigator: Zhi Yan, M.D.         
Maoming Traditional Chinese Medical Hospital Recruiting
Maoming, Guangdong, China
Contact: Dongrun Yan, M.D.       1792191@qq.com   
Principal Investigator: Wenguo Huang, M.D.         
China, Hainan
Hainan Provincial Hospital of Traditional Chinese Medicine Recruiting
Haikou, Hainan, China, 570100
Contact: Guangfeng Zhao, M.D.    +8613700410380    408195770@qq.com   
Principal Investigator: Guohu Weng, M.D.         
Haikou People's Hospital Recruiting
Haikou, Hainan, China, 570208
Contact: Guoshuai Yang, M.D.    +86-13876006248    youngester4213@sina.com   
Principal Investigator: Guoshuai Yang, M.D.         
China, Jiangsu
The First Affiliated Hospital of Wenzhou Medical University Recruiting
Wenzhou, Jiangsu, China, 325000
Contact: Saijun Zhou, M.D.    +8613857746659    2498093074@qq.com   
Principal Investigator: Xu Zhang, M.D.         
Sponsors and Collaborators
Nanfang Hospital of Southern Medical University
Investigators
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Principal Investigator: Suyue Pan, M.D., Ph.D. Department of Neurology, Nanfang Hospital, Southern Medical University

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Responsible Party: Nanfang Hospital of Southern Medical University
ClinicalTrials.gov Identifier: NCT03284463     History of Changes
Other Study ID Numbers: NFEC-2017-130
First Posted: September 15, 2017    Key Record Dates
Last Update Posted: June 6, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Nanfang Hospital of Southern Medical University:
acute ischemic stroke
glibenclamide
rt-PA
blood-brain barrier
brain edema
Additional relevant MeSH terms:
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Stroke
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs