<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03284463</url>
  </required_header>
  <id_info>
    <org_study_id>NFEC-2017-130</org_study_id>
    <nct_id>NCT03284463</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Glibenclamide Combined With Rt-PA in Acute Cerebral Embolism</brief_title>
  <acronym>SE-GRACE</acronym>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nanfang Hospital, Southern Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nanfang Hospital, Southern Medical University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to evaluate the safety and efficacy of oral glibenclamide in acute&#xD;
      ischemic stroke patients who under intravenous rt-PA thrombolysis.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">May 28, 2023</completion_date>
  <primary_completion_date type="Actual">August 28, 2022</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points</measure>
    <time_frame>90 days after the stroke onset</time_frame>
    <description>The proportion of mordified Rankin Scale of 0 to 2 points at 90 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Early improvement: The proportion of NIHSS decreased ≥ 4 points</measure>
    <time_frame>7 days after the stroke onset</time_frame>
    <description>The proportion of NIHSS decreased ≥ 4 points at 7 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT</measure>
    <time_frame>96 hours after the stroke onset</time_frame>
    <description>The proportion of parenchymal hemorrhagic transformation in cranial CT within 96 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Midline shift: The proportion of midline shift ≥ 6 mm in cranial CT</measure>
    <time_frame>96 hours after the stroke onset</time_frame>
    <description>The proportion of midline shift ≥ 6 mm in cranial CT within 96 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome 2: The modified Rankin Scale distribution</measure>
    <time_frame>90 days after the stroke onset</time_frame>
    <description>The modified Rankin Scale distribution at 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome 3: The proportion of Barthel Index of 60-100 points</measure>
    <time_frame>90 days after the stroke onset</time_frame>
    <description>The proportion of Barthel Index of 60-100 points</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional outcome 4: The proportion of IQCODE of ≤ 3.40</measure>
    <time_frame>6 months and 1 year after the stroke onset</time_frame>
    <description>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</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood-brain barrier: The serum concentration of MMP-9</measure>
    <time_frame>Baseline, 24, 48, and 72 hours after the stroke onset</time_frame>
    <description>The serum concentration of MMP-9 at baseline, and at 24, 48, and 72 h</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mortality</measure>
    <time_frame>90 days after the stroke onset</time_frame>
    <description>The mortality at 90 days</description>
  </other_outcome>
  <other_outcome>
    <measure>Early neurological deterioration</measure>
    <time_frame>24 hours after the stroke onset</time_frame>
    <description>The ratio of neurological deterioration (NIHSS increased ≥ 4 points) within 24 hours after the onset</description>
  </other_outcome>
  <other_outcome>
    <measure>Hypoglycemia</measure>
    <time_frame>5 days after the stroke onset</time_frame>
    <description>The incidence of hypoglycemia (random blood glucose &lt; 3.9 mmol/L)</description>
  </other_outcome>
  <other_outcome>
    <measure>Cardiac events</measure>
    <time_frame>30 days after the stroke onset</time_frame>
    <description>The incidence of cardiac events in cardiac examination (ECG, echocardiography)</description>
  </other_outcome>
  <other_outcome>
    <measure>Pulmonary infection</measure>
    <time_frame>7 days within the stroke onset</time_frame>
    <description>The incidence of pulmonary infection</description>
  </other_outcome>
  <other_outcome>
    <measure>AEs and SAEs</measure>
    <time_frame>30 days after the stroke onset</time_frame>
    <description>The incidence of adverse event and serious adverse event</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">306</enrollment>
  <condition>Acute Stroke</condition>
  <arm_group>
    <arm_group_label>Glibenclamide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Glibenclamide Tablets</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo for Glibenclamide</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glibenclamide</intervention_name>
    <description>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.</description>
    <arm_group_label>Glibenclamide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>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.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA&#xD;
             territory involvement in addition to primary MCA territory stroke is acceptable)&#xD;
&#xD;
          -  Aged ≥18 and ≤74 years&#xD;
&#xD;
          -  A baseline NIHSS score between 4 to 25&#xD;
&#xD;
          -  Intravenous rt-PA thrombolysis conducted within 4.5 hours after stroke onset, if&#xD;
             known, or the time last seen well [termed &quot;time last known at neurologic baseline&quot;&#xD;
             (TLK@B)]&#xD;
&#xD;
          -  The time to the start of administration of Study Drug must be ≤10 h after time of&#xD;
             symptom onset or TLK@B&#xD;
&#xD;
          -  Informed consent was signed by the subject or the legal representative&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior to stroke, significant disability exists, with modified Rankin Scale &gt;1 point&#xD;
&#xD;
          -  With medical history or evidence of cerebral hemorrhage, subarachnoid hemorrhage,&#xD;
             arteriovenous malformation, cerebral aneurysm or brain tumor&#xD;
&#xD;
          -  With clinical or imaging evidence of contralateral cerebral infarction which is&#xD;
             believed to have influence on the patient outcome by the investigators&#xD;
&#xD;
          -  With clinical or imaging evidence of occlusion in vertebral or basilar artery&#xD;
&#xD;
          -  With clinical evidence of brain herniation, e.g., one or two dilated, fixed pupils;&#xD;
             unconsciousness (i.e., C2 on item 1a on the NIHSS); and/or loss of other brainstem&#xD;
             reflexes, attributable to edema or herniation according to the investigator's judgment&#xD;
&#xD;
          -  With gastrointestinal bleeding and instable hemodynamics or other causes that force&#xD;
             the patient to stop nutritional support&#xD;
&#xD;
          -  Renal disorder from the patient's history (e.g., dialysis) or eGFR of &lt;60 mL/min/1.73&#xD;
             m2&#xD;
&#xD;
          -  Severe liver disease, or ALT &gt;3 times upper limit of normal or bilirubin &gt;2 times&#xD;
             normal (subjects may be randomized if liver function tests have been drawn but are not&#xD;
             yet available and the subject has no known history of liver disease; however treatment&#xD;
             with Study Drug cannot commence until liver function tests are available and indicate&#xD;
             ALT &gt;3 times upper limit of normal and bilirubin &gt;2 times upper limit of normal)&#xD;
&#xD;
          -  Blood glucose &lt;3.0 mmol/L at enrollment or immediately prior to administration of&#xD;
             Study Drug, or a clinically significant history of hypoglycemia&#xD;
&#xD;
          -  Acute ST elevation myocardial infarction, and/or acute decompensated heart failure,&#xD;
             and/or Tc &gt; 520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole),&#xD;
             and/or admission for an acute coronary syndrome, myocardial infarction, or coronary&#xD;
             intervention within the past 3 months&#xD;
&#xD;
          -  Known sulfonylurea treatment within 7 days. Sulfonylureas include&#xD;
             glyburide/glibenclamide; glibenclamide plus metformin; Xiaoke Pill (a Chinese patent&#xD;
             medicine with main effective constituent of glibenclamide); glimepiride; repaglinide;&#xD;
             nateglinide; glipizide; gliclazide; tolbutamide; glibornuride&#xD;
&#xD;
          -  Known treatment with bosentan within 7 days&#xD;
&#xD;
          -  Known allergy to sulfa or specific allergy to sulfonylurea drugs&#xD;
&#xD;
          -  Known G6PD enzyme deficiency&#xD;
&#xD;
          -  Pregnant women. Women must be either postmenopausal (as confirmed by the LAR),&#xD;
             permanently sterilized or, if ≤50 years old must have a negative test for pregnancy&#xD;
             obtained before enrollment&#xD;
&#xD;
          -  Breast-feeding women who do not agree (or their LAR does not agree) to stop&#xD;
             breastfeeding during Study Drug infusion and for 7 days following the end of Study&#xD;
             Drug infusion&#xD;
&#xD;
          -  Patients already enrolled in a non-observation-only stroke study, or with&#xD;
             life-expectancy &lt;6 months not related to current stroke, or those unlikely to be&#xD;
             compliant with follow up&#xD;
&#xD;
          -  Patients currently receiving an investigational drug&#xD;
&#xD;
          -  Mentally incompetent (prior to qualifying stroke) patients and wards of the state&#xD;
&#xD;
          -  Patients who, in the opinion of the investigator, are not suitable for the study&#xD;
             (reason to be documented)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>74 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Suyue Pan, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Department of Neurology, Nanfang Hospital, Southern Medical University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Huadu District People's Hospital of Guangzhou</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <zip>510515</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nanfang Hospital of Southern Medical University</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Heyuan People's Hospital</name>
      <address>
        <city>Heyuan</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maoming People's Hospital</name>
      <address>
        <city>Maoming</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maoming Traditional Chinese Medical Hospital</name>
      <address>
        <city>Maoming</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hainan Provincial Hospital of Traditional Chinese Medicine</name>
      <address>
        <city>Haikou</city>
        <state>Hainan</state>
        <zip>570100</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Haikou People's Hospital</name>
      <address>
        <city>Haikou</city>
        <state>Hainan</state>
        <zip>570208</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Affiliated Hospital of Wenzhou Medical University</name>
      <address>
        <city>Wenzhou</city>
        <state>Jiangsu</state>
        <zip>325000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>September 14, 2017</study_first_submitted>
  <study_first_submitted_qc>September 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>June 9, 2023</last_update_submitted>
  <last_update_submitted_qc>June 9, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>acute ischemic stroke</keyword>
  <keyword>glibenclamide</keyword>
  <keyword>rt-PA</keyword>
  <keyword>blood-brain barrier</keyword>
  <keyword>brain edema</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glyburide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03284463
org study id: NFEC-2017-130
nct id: NCT03284463
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This study is designed to evaluate the safety and efficacy of oral glibenclamide in acute
      ischemic stroke patients who under intravenous rt-PA thrombolysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points
time frame: 90 days after the stroke onset
description: The proportion of mordified Rankin Scale of 0 to 2 points at 90 days
measure: Early improvement: The proportion of NIHSS decreased ≥ 4 points
time frame: 7 days after the stroke onset
description: The proportion of NIHSS decreased ≥ 4 points at 7 days
measure: Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT
time frame: 96 hours after the stroke onset
description: The proportion of parenchymal hemorrhagic transformation in cranial CT within 96 hours
measure: Midline shift: The proportion of midline shift ≥ 6 mm in cranial CT
time frame: 96 hours after the stroke onset
description: The proportion of midline shift ≥ 6 mm in cranial CT within 96 hours
measure: Functional outcome 2: The modified Rankin Scale distribution
time frame: 90 days after the stroke onset
description: The modified Rankin Scale distribution at 90 days
measure: Functional outcome 3: The proportion of Barthel Index of 60-100 points
time frame: 90 days after the stroke onset
description: The proportion of Barthel Index of 60-100 points
measure: Functional outcome 4: The proportion of IQCODE of ≤ 3.40
time frame: 6 months and 1 year after the stroke onset
description: 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
measure: Blood-brain barrier: The serum concentration of MMP-9
time frame: Baseline, 24, 48, and 72 hours after the stroke onset
description: The serum concentration of MMP-9 at baseline, and at 24, 48, and 72 h
measure: Mortality
time frame: 90 days after the stroke onset
description: The mortality at 90 days
measure: Early neurological deterioration
time frame: 24 hours after the stroke onset
description: The ratio of neurological deterioration (NIHSS increased ≥ 4 points) within 24 hours after the onset
measure: Hypoglycemia
time frame: 5 days after the stroke onset
description: The incidence of hypoglycemia (random blood glucose < 3.9 mmol/L)
measure: Cardiac events
time frame: 30 days after the stroke onset
description: The incidence of cardiac events in cardiac examination (ECG, echocardiography)
measure: Pulmonary infection
time frame: 7 days within the stroke onset
description: The incidence of pulmonary infection
measure: AEs and SAEs
time frame: 30 days after the stroke onset
description: The incidence of adverse event and serious adverse event
arm group label: Glibenclamide
arm group type: Active Comparator
description: Glibenclamide Tablets
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo for Glibenclamide
intervention type: Drug
intervention name: Glibenclamide
description: 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.
arm group label: Glibenclamide
intervention type: Drug
intervention name: Placebo
description: 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.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 74 Years
healthy volunteers: No
last name: Suyue Pan, M.D., Ph.D.
role: Principal Investigator
affiliation: Department of Neurology, Nanfang Hospital, Southern Medical University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
responsible party type: Sponsor
mesh term: Stroke
mesh term: Glyburide
sharing ipd: No