<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/NCT04454788</url>
  </required_header>
  <id_info>
    <org_study_id>2019.125</org_study_id>
    <nct_id>NCT04454788</nct_id>
  </id_info>
  <brief_title>Extending the Time Window for Tenecteplase by Effective Reperfusion in Patients With Large Vessel Occlusion</brief_title>
  <acronym>ETERNAL-LVO</acronym>
  <official_title>Extending the Time Window for Tenecteplase by Effective Reperfusion of peNumbrAL Tissue in Patients With Large Vessel Occlusion</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Melbourne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Professor Mark Parsons</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Melbourne</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>
      Patients presenting to the emergency department with an acute ischemic stroke due to a large&#xD;
      vessel occlusion eligible for thrombectomy and target mismatch on computed tomography&#xD;
      perfusion imaging within 24 hours of onset will be assessed determine their eligibility for&#xD;
      randomization into the trial. If the patient gives informed consent they will be randomised&#xD;
      using a central computerised allocation process to either standard of care (no intravenous&#xD;
      thrombolytic treatment or intravenous alteplase 0.9mg/kg) or tenecteplase before undergoing&#xD;
      intra-arterial clot retrieval. The trial is prospective, randomised, open-label, blinded&#xD;
      endpoint (PROBE) design.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">August 1, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2025</primary_completion_date>
  <phase>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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS</measure>
    <time_frame>90 days</time_frame>
    <description>Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2) at 90 days</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Early clinical improvement</measure>
    <time_frame>24 hours</time_frame>
    <description>Reduction in National Institutes of Health Stroke Scale (NIHSS) score of ≥8 points at 24 hours or reaching NIHSS 0-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale (mRS) 0-2 (functional independence)</measure>
    <time_frame>90 days</time_frame>
    <description>Modified Rankin Scale (mRS) 0-2 (functional independence) at 90 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Substantial reperfusion at initial angiographic assessment</measure>
    <time_frame>initial angiography within 24 hours of stroke onset</time_frame>
    <description>Proportion of patients with &gt;50% reperfusion of the affected vascular territory (mTICI 3b/3) on initial digital subtraction angiography prior to thrombectomy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptomatic intracerebral hemorrhage (sICH)</measure>
    <time_frame>24 hours post-randomization</time_frame>
    <description>sICH defined as parenchymal hematoma type 2 (PH2) - blood clot occupying &gt;30% of the infarcted territory with substantial mass effect</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Death due to any cause</measure>
    <time_frame>90 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rankin Scale (mRS) 5-6</measure>
    <time_frame>90 days</time_frame>
    <description>Poor functional outcome of death or requirement for fulltime nursing care</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Successful reperfusion at 24 hours</measure>
    <time_frame>24 hours</time_frame>
    <description>Reperfusion (defined as &gt;90% and &gt;50% reduction in perfusion lesion volume)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Infarct growth</measure>
    <time_frame>24 hours</time_frame>
    <description>Increase in the volume of irreversibly injured brain between pre-treatment and 24 hour imaging</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recanalization</measure>
    <time_frame>24 hours</time_frame>
    <description>Change in vessel patency between pre-treatment and 24h imaging (CT or MR angiography)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">740</enrollment>
  <condition>Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Intravenous tenecteplase (TNK)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Intravenous tissue plasminogen activator (tPA)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenecteplase</intervention_name>
    <description>Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as intravenous bolus over 5-10 seconds</description>
    <arm_group_label>Intravenous tenecteplase (TNK)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard Care (which may include intravenous Alteplase)</intervention_name>
    <description>Patients will receive standard care which may include intravenous alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.</description>
    <arm_group_label>Intravenous tissue plasminogen activator (tPA)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients presenting with acute hemispheric ischemic stroke with onset (or the time&#xD;
             they last known to be well) within 24 hours.&#xD;
&#xD;
          -  Patient's age is ≥18 years.&#xD;
&#xD;
          -  Premorbid mRS &lt;3, with a concurrent assessment of whether the patient was able,&#xD;
             immediately prior to the stroke, to: 1) Drive, or (if never drives) perform own&#xD;
             Domestic duties, and 2) Shop for themselves, and 3) Bank/do their own finances (i.e.&#xD;
             Drive/Domestic, Bank, Shop = DBS +ve). Need to be DBS +ve to be study eligible.&#xD;
&#xD;
          -  Presence of a vessel occlusion on CTA or MRA. LVO will be defined as 'potentially&#xD;
             retrievable' thrombus at one or more of the following sites: intracranial internal&#xD;
             carotid (ICA), middle cerebral artery (MCA) first segment (M1), proximal middle&#xD;
             cerebral artery second segment (M2) or isolated/tandem occlusion of the extracranial&#xD;
             ICA. Patients with an extracranial ICA stenosis and occlusion are also eligible.&#xD;
&#xD;
          -  Presence of 'target mismatch' on automated perfusion CT (CTP) or diffusion-perfusion&#xD;
             MRI software defined as an ischemic core of &lt;70mL, penumbra of &gt;20mL and an ischemic&#xD;
             core to perfusion lesion ratio of &gt;1.8&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Intracranial hemorrhage (ICH) or other diagnosis (e.g. tumor).&#xD;
&#xD;
          -  Basilar Artery occlusion.&#xD;
&#xD;
          -  Extensive early ischemic change (hypodensity on NCCT or high signal on DWI-MRI) or&#xD;
             early ischemic change outside the perfusion lesion that invalidates mismatch criteria.&#xD;
&#xD;
          -  Pre-stroke mRS score of &gt; 2 (indicating significant previous disability) or DBS -ve.&#xD;
&#xD;
          -  Any terminal illness such that patient would not be expected to survive more than 1&#xD;
             year&#xD;
&#xD;
          -  Any condition that, in the judgment of the investigator could impose hazards to the&#xD;
             patient if study therapy is initiated or affect the participation of the patient in&#xD;
             the study.&#xD;
&#xD;
          -  Pregnant women.&#xD;
&#xD;
          -  Other standard contraindications to thrombolysis.&#xD;
&#xD;
          -  Minor stroke symptoms, or major stroke symptoms rapidly improving&#xD;
&#xD;
          -  Clinical presentation suggesting subarachnoid haemorrhage&#xD;
&#xD;
          -  Known bleeding diasthesis and/or platelet count &lt;100,000 or taking warfarin with INR &gt;&#xD;
             1.7.&#xD;
&#xD;
          -  Patients who have received heparin within 48 hours must have normal aPTT.&#xD;
&#xD;
          -  Major surgery or serious trauma within 14 days, serious head trauma within 3 months.&#xD;
&#xD;
          -  GI or urinary tract haemorrhage within last 21 days&#xD;
&#xD;
          -  Arterial puncture at a non-compressible site or lumbar puncture within 7 days&#xD;
&#xD;
          -  Systolic BP &gt; 185, diastolic BP &gt; 110mmHg&#xD;
&#xD;
          -  Clinical stroke within 3 months or history of ICH&#xD;
&#xD;
          -  Unable to gain consent from patient or person responsible&#xD;
&#xD;
          -  Known severe renal impairment (GFR &lt; 15mls/min)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Andrew Bivard, PHD</last_name>
    <phone>+6193424424</phone>
    <email>abivard@unimelb.edu.au</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Amy McDonald, BN</last_name>
    <phone>+6193424424</phone>
    <email>amym1@unimelb.edu.au</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Liverpool Hospital</name>
      <address>
        <city>Liverpool</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dennis Cordato</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>John Hunter Hospital</name>
      <address>
        <city>Newcastle</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michelle Russell</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Randwick</city>
        <state>New South Wales</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ken Butcher</last_name>
      <email>ken.butcher@unsw.edu.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Princess Alexandra Hospital</name>
      <address>
        <city>Woolloongabba 4102</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Helen Brown</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Adelaide Hospital</name>
      <address>
        <city>Adelaide</city>
        <state>South Australia</state>
        <zip>5000</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tim Kleinig</last_name>
      <email>tim.kleinig@sa.gov.au</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Royal Melbourne Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amy McDonald</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Box Hill Hospital</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <country>Australia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Phillip Choi</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>June 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>June 15, 2021</last_update_submitted>
  <last_update_submitted_qc>June 15, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Melbourne</investigator_affiliation>
    <investigator_full_name>Bruce Campbell</investigator_full_name>
    <investigator_title>Prof</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ischemic Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tissue Plasminogen Activator</mesh_term>
    <mesh_term>Tenecteplase</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/NCT04454788
org study id: 2019.125
nct id: NCT04454788
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Patients presenting to the emergency department with an acute ischemic stroke due to a large
      vessel occlusion eligible for thrombectomy and target mismatch on computed tomography
      perfusion imaging within 24 hours of onset will be assessed determine their eligibility for
      randomization into the trial. If the patient gives informed consent they will be randomised
      using a central computerised allocation process to either standard of care (no intravenous
      thrombolytic treatment or intravenous alteplase 0.9mg/kg) or tenecteplase before undergoing
      intra-arterial clot retrieval. The trial is prospective, randomised, open-label, blinded
      endpoint (PROBE) design.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS
time frame: 90 days
description: Modified Rankin Scale (mRS) 0-1 (no disability) or return to baseline mRS (if baseline premorbid mRS =2) at 90 days
measure: Early clinical improvement
time frame: 24 hours
description: Reduction in National Institutes of Health Stroke Scale (NIHSS) score of ≥8 points at 24 hours or reaching NIHSS 0-1
measure: Modified Rankin Scale (mRS) 0-2 (functional independence)
time frame: 90 days
description: Modified Rankin Scale (mRS) 0-2 (functional independence) at 90 days
measure: Substantial reperfusion at initial angiographic assessment
time frame: initial angiography within 24 hours of stroke onset
description: Proportion of patients with >50% reperfusion of the affected vascular territory (mTICI 3b/3) on initial digital subtraction angiography prior to thrombectomy
measure: Symptomatic intracerebral hemorrhage (sICH)
time frame: 24 hours post-randomization
description: sICH defined as parenchymal hematoma type 2 (PH2) - blood clot occupying >30% of the infarcted territory with substantial mass effect
measure: Death due to any cause
time frame: 90 days
measure: Modified Rankin Scale (mRS) 5-6
time frame: 90 days
description: Poor functional outcome of death or requirement for fulltime nursing care
measure: Successful reperfusion at 24 hours
time frame: 24 hours
description: Reperfusion (defined as >90% and >50% reduction in perfusion lesion volume)
measure: Infarct growth
time frame: 24 hours
description: Increase in the volume of irreversibly injured brain between pre-treatment and 24 hour imaging
measure: Recanalization
time frame: 24 hours
description: Change in vessel patency between pre-treatment and 24h imaging (CT or MR angiography)
arm group label: Intravenous tenecteplase (TNK)
arm group type: Experimental
description: Patients will receive intravenous tenecteplase (0.25mg/kg, maximum 25mg, administered as a bolus over 5-10 seconds).
arm group label: Intravenous tissue plasminogen activator (tPA)
arm group type: Active Comparator
description: Patients will receive standard of care (no intravenous thrombolytic treatment or intravenous alteplase 0.9mg/kg at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.
intervention type: Drug
intervention name: Tenecteplase
description: Genetically modified tissue plasminogen activator at a dose of 0.25mg/kg given as intravenous bolus over 5-10 seconds
arm group label: Intravenous tenecteplase (TNK)
intervention type: Drug
intervention name: Standard Care (which may include intravenous Alteplase)
description: Patients will receive standard care which may include intravenous alteplase at the standard licensed dose of 0.9 mg/kg up to a maximum of 90mg, 10% as bolus and the remainder over 1 hour.
arm group label: Intravenous tissue plasminogen activator (tPA)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andrew Bivard, PHD
phone: +6193424424
email: abivard@unimelb.edu.au
last name: Amy McDonald, BN
phone: +6193424424
email: amym1@unimelb.edu.au
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: University of Melbourne
investigator full name: Bruce Campbell
investigator title: Prof
mesh term: Ischemic Stroke
mesh term: Tissue Plasminogen Activator
mesh term: Tenecteplase
sharing ipd: No