xml: <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/NCT06010628</url>
    </required_header>
    <id_info>
      <org_study_id>Y (2023) 144</org_study_id>
      <nct_id>NCT06010628</nct_id>
    </id_info>
    <brief_title>Tenecteplase Plus Butylphthalide for Acute Ischemic Stroke Within 4.5 to 6 Hours of Onset (EXIT-BT2)</brief_title>
    <official_title>Tenecteplase Plus Butylphthalide for Acute Ischemic Stroke Within 4.5 to 6 Hours of Onset (EXIT-BT2): a Prospective, Randomized, Open Label, Blinded Endpoint, and Multi-center Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>General Hospital of Shenyang Military Region</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>General Hospital of Shenyang Military Region</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        To date, the benefit of intravenous thrombolysis is confined within 4.5 hours of onset for&#xD;
        acute ischemic stroke (AIS) patients without advanced neuroimaging selection. Unpublished&#xD;
        pilot EXIT-BT (EXtending the tIme window of Thrombolysis by ButylphThalide up to 6 Hours&#xD;
        after onset) suggest the safety, feasibility and potential benefit of intravenous&#xD;
        tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 hours of onset.&#xD;
        The current study aims to investigate the efficacy and safety of TNK plus NBP for AIS within&#xD;
        4.5 to 6 hours of onset.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 15, 2023</start_date>
    <completion_date type="Anticipated">March 15, 2025</completion_date>
    <primary_completion_date type="Anticipated">March 15, 2025</primary_completion_date>
    <phase>Phase 4</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>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>proportion of modified Rankin Scale (mRS) 0-1</measure>
      <time_frame>90±7 days</time_frame>
      <description>The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>proportion of modified Rankin Scale (mRS) 0-2</measure>
      <time_frame>90±7 days</time_frame>
      <description>The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ordinal distribution of modified Rankin Scale (mRS)</measure>
      <time_frame>90±7 days</time_frame>
      <description>The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>change in National Institute of Health stroke scale (NIHSS) score</measure>
      <time_frame>24 (-6/+12) hours</time_frame>
      <description>the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>change in National Institute of Health stroke scale (NIHSS) score</measure>
      <time_frame>10±2 days</time_frame>
      <description>the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>occurrence of early neurological improvement (ENI)</measure>
      <time_frame>24 (-6/+12) hours</time_frame>
      <description>ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>new stroke or other vascular event(s)</measure>
      <time_frame>90±7 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>all-cause mortality</measure>
      <time_frame>90±7 days</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>symptomatic intracranial hemorrhage</measure>
      <time_frame>24 (-6/+12) hours</time_frame>
      <description>any evidence of bleeding on the head CT scan associated with clinically significant neurological deterioration (NIHSS score ≥4 points increase)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>intracranial hemorrhage</measure>
      <time_frame>24 (-6/+12) hours</time_frame>
      <description>any evidence of bleeding on the head CT scan, classified by the Heidelberg Bleeding Classification</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>major systemic bleeding event</measure>
      <time_frame>24 (-6/+12) hours</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>any bleeding event</measure>
      <time_frame>24 (-6/+12) hours</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">1250</enrollment>
    <condition>Stroke, Ischemic</condition>
    <arm_group>
      <arm_group_label>Tenecteplase group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>intravenous thrombolysis with tenecteplase, combined with butylphthalide.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>standard stroke care based on national guideline</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tenecteplase</intervention_name>
      <description>intravenous butylphthalide (NBP) (25mg, 100 mL sodium chloride injection) and tenecteplase (0.25 mg/kg, a single bolus over 5 to 10 seconds, a maximum of 25 mg), followed by intravenous NBP (25mg, 100 mL sodium chloride injection, two times daily for 10±2 days). This will be later followed by oral soft NBP capsules (0.2 g, three times daily for the next 80±2 days)</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Tenecteplase group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age ≥ 18 year&#xD;
  &#xD;
            -  Acute ischemic stroke confirmed by non-contrast computed tomography;&#xD;
  &#xD;
            -  The time from last known well to treatment: 4.5 - 6 hours;&#xD;
  &#xD;
            -  NIHSS ≥ 4 at randomization;&#xD;
  &#xD;
            -  First stroke onset or past stroke without obvious neurological deficit (mRS≤2);&#xD;
  &#xD;
            -  Signed informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pre-stroke disability (mRS≥3);&#xD;
  &#xD;
            -  Planned intravenous thrombolysis based on WAKE-UP or EXTEND study criterion;&#xD;
  &#xD;
            -  Any contraindication to intravenous thrombolysis: Obvious head injury or stroke within&#xD;
               3 months; Subarachnoid or intracranial hemorrhage; History of intracranial hemorrhage;&#xD;
               Intracranial tumor, arteriovenous malformation or aneurysm; Intracranial or spinal&#xD;
               cord surgery within 3 months; Myocardial infarction within 3 months; Major surgery&#xD;
               within 1 month; Gastrointestinal or urinary tract hemorrhage within the previous 30&#xD;
               days; Arterial puncture at a noncompressible site within the previous seven days;&#xD;
               Active internal hemorrhage; Coagulation abnormalities: platelet count of &lt;100000/mm3;&#xD;
               Aortic arch dissection; Heparin therapy within 24 hours; Infective endocarditis; Oral&#xD;
               warfarin is being taken and INR&gt;1.6 or APTT abnormal; Systolic pressure ≥185 mmHg or&#xD;
               diastolic pressure ≥110 mmHg; Blood glucose &lt; 50 mg/dl (2.7mmol/L); Neurological&#xD;
               deficit after epileptic seizures;&#xD;
  &#xD;
            -  Pregnancy;&#xD;
  &#xD;
            -  Allergy to test drugs;&#xD;
  &#xD;
            -  Comorbidity with other serious diseases;&#xD;
  &#xD;
            -  Participating in other clinical trials within 3 months;&#xD;
  &#xD;
            -  Patients not suitable for the study considered by researcher.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Department of Neurology, General Hospital of Northern Theater Command</name>
        <address>
          <city>Shenyang</city>
          <zip>110016</zip>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 20, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 24, 2023</study_first_posted>
    <last_update_submitted>August 23, 2023</last_update_submitted>
    <last_update_submitted_qc>August 23, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 25, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>General Hospital of Shenyang Military Region</investigator_affiliation>
      <investigator_full_name>Hui-Sheng Chen</investigator_full_name>
      <investigator_title>Director</investigator_title>
    </responsible_party>
    <keyword>thrombolysis</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Stroke</mesh_term>
      <mesh_term>Ischemic Stroke</mesh_term>
      <mesh_term>Ischemia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Tenecteplase</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06010628
  org study id: Y (2023) 144
  nct id: NCT06010628
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  To date, the benefit of intravenous thrombolysis is confined within 4.5 hours of onset for
        acute ischemic stroke (AIS) patients without advanced neuroimaging selection. Unpublished
        pilot EXIT-BT (EXtending the tIme window of Thrombolysis by ButylphThalide up to 6 Hours
        after onset) suggest the safety, feasibility and potential benefit of intravenous
        tenecteplase (TNK) plus Dl-3-n-Butylphthalide (NBP) in AIS within 4.5 to 6 hours of onset.
        The current study aims to investigate the efficacy and safety of TNK plus NBP for AIS within
        4.5 to 6 hours of onset.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: proportion of modified Rankin Scale (mRS) 0-1
  time frame: 90±7 days
  description: The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
  measure: proportion of modified Rankin Scale (mRS) 0-2
  time frame: 90±7 days
  description: The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
  measure: ordinal distribution of modified Rankin Scale (mRS)
  time frame: 90±7 days
  description: The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
  measure: change in National Institute of Health stroke scale (NIHSS) score
  time frame: 24 (-6/+12) hours
  description: the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome.
  measure: change in National Institute of Health stroke scale (NIHSS) score
  time frame: 10±2 days
  description: the minimum and maximum values of NIHSS are 0 and 42, respectively; higher NIHSS mean a worse outcome.
  measure: occurrence of early neurological improvement (ENI)
  time frame: 24 (-6/+12) hours
  description: ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score
  measure: new stroke or other vascular event(s)
  time frame: 90±7 days
  measure: all-cause mortality
  time frame: 90±7 days
  measure: symptomatic intracranial hemorrhage
  time frame: 24 (-6/+12) hours
  description: any evidence of bleeding on the head CT scan associated with clinically significant neurological deterioration (NIHSS score ≥4 points increase)
  measure: intracranial hemorrhage
  time frame: 24 (-6/+12) hours
  description: any evidence of bleeding on the head CT scan, classified by the Heidelberg Bleeding Classification
  measure: major systemic bleeding event
  time frame: 24 (-6/+12) hours
  measure: any bleeding event
  time frame: 24 (-6/+12) hours
  arm group label: Tenecteplase group
  arm group type: Experimental
  description: intravenous thrombolysis with tenecteplase, combined with butylphthalide.
  arm group label: Control group
  arm group type: Other
  description: standard stroke care based on national guideline
  intervention type: Drug
  intervention name: Tenecteplase
  description: intravenous butylphthalide (NBP) (25mg, 100 mL sodium chloride injection) and tenecteplase (0.25 mg/kg, a single bolus over 5 to 10 seconds, a maximum of 25 mg), followed by intravenous NBP (25mg, 100 mL sodium chloride injection, two times daily for 10±2 days). This will be later followed by oral soft NBP capsules (0.2 g, three times daily for the next 80±2 days)
  arm group label: Control group
  arm group label: Tenecteplase group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: General Hospital of Shenyang Military Region
  investigator full name: Hui-Sheng Chen
  investigator title: Director
  mesh term: Stroke
  mesh term: Ischemic Stroke
  mesh term: Ischemia
  mesh term: Tenecteplase
  sharing ipd: Undecided