<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/NCT03785678</url>
  </required_header>
  <id_info>
    <org_study_id>ML40787</org_study_id>
    <nct_id>NCT03785678</nct_id>
  </id_info>
  <brief_title>Tenecteplase in Stroke Patients Between 4.5 and 24 Hours</brief_title>
  <acronym>TIMELESS</acronym>
  <official_title>A Phase III, Prospective, Double-blind, Randomized, Placebo-controlled Trial of Thrombolysis in Imaging-eligible, Late-window Patients to Assess the Efficacy and Safety of Tenecteplase (TIMELESS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genentech, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the efficacy and safety of tenecteplase compared with placebo in&#xD;
      participants with acute ischemic stroke (AIS).&#xD;
&#xD;
      All participants will receive standard-of-care therapy according to AmericanHeart&#xD;
      Association/American Stroke Association clinical guidelines (2018). To determine eligibility&#xD;
      for randomization, all participants will undergo multimodal CT or MRI at baseline. Only&#xD;
      participants with a vessel occlusion (ICA or MCA M1/M2) and penumbral tissue will be&#xD;
      randomized. The primary analysis is to compare the efficacy of tenecteplase versus placebo in&#xD;
      all participants at Day 90.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 2, 2019</start_date>
  <completion_date type="Actual">February 28, 2023</completion_date>
  <primary_completion_date type="Actual">February 28, 2023</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ordinal modified Rankin scale (mRS) score</measure>
    <time_frame>Day 90</time_frame>
    <description>The Efficacy of Tenecteplase compared to placebo is evaluated in terms of Ordinal mRS score at day 90.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with functional independence</measure>
    <time_frame>Day 90</time_frame>
    <description>The efficacy of Tenecteplase is evaluated in terms of proportion of patients with functional independence, defined as an mRS of 0-2, at Day 90</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with angiographic reperfusion</measure>
    <time_frame>Day 1</time_frame>
    <description>The efficacy of Tenecteplase is evaluated in terms of proportion of patients with angiographic reperfusion at completion of angiographic procedure (endovascular patients only).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median NIHSS score</measure>
    <time_frame>Day 90</time_frame>
    <description>The efficacy of Tenecteplase is evaluted in terms of Median NIHSS score at Day 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with a Barthel Index (BI) score &gt;=95</measure>
    <time_frame>Day 90</time_frame>
    <description>The efficacy of Tenecteplase is evaluated in terms of Proportion of patients with a BI score &gt;=95 at Day 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with good recovery based on the Glasgow Outcome Scale (GOS) at Day 90</measure>
    <time_frame>Day 90</time_frame>
    <description>The efficacy of Tenecteplase is evaluated in terms of the proportion of patients with good recovery based on the GOS at Day 90.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with reperfusion at 24 hours post-randomization</measure>
    <time_frame>Day 2</time_frame>
    <description>The efficacy of Tenecteplase is evaluated in terms of proportion of patients with reperfusion at 24 hours post-randomization, defined as &gt;90% reduction in Tmax&gt;6s lesion volume</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with recanalization at 24 hours post-randomization</measure>
    <time_frame>Day 2</time_frame>
    <description>The efficacy of Tenecteplase is evaluated in terms of proportion of patients with recanalization at 24 hours post-randomization, defined as complete or partial recanalization on CT angiography (CTA)/magnetic resonance angiography (MRA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with symptomatic intracranial hemorrhage (sICH a)</measure>
    <time_frame>Day 2</time_frame>
    <description>The safety profile of Tenecteplase is evaluated in terms of number of patients with sICH within 36 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence and severity of adverse events</measure>
    <time_frame>From baseline up to day 90</time_frame>
    <description>The safety profile of Tenecteplase is evaluated in terms of incidence and severity of adverse events.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality rate up to Day 30 and Day 90</measure>
    <time_frame>Day 30 and Day 90</time_frame>
    <description>The safety profile of Tenecteplase is evaluated in terms of mortality rate up to Day 30 and Day 90</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with parenchymal hematoma type 2 (PH2) at the 72-96 hour visit</measure>
    <time_frame>Day 3</time_frame>
    <description>The safety profile of Tenecteplase is evaluated in terms of proportion of patients with PH2 at the 72-96 hour visit</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">452</enrollment>
  <condition>THROMBOLYSIS</condition>
  <arm_group>
    <arm_group_label>Tenecteplase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients in this arm will receive Tenecteplase (0.25 mg/kg, maximum 25 mg) administered as a single bolus injection over 5 seconds.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients in this arm will receive placebo administered as a single bolus injection over 5 seconds.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Tenecteplase</intervention_name>
    <description>The investigational medicinal product (IMP) for this study is tenecteplase. The recommended total dose for this study is weight-based with 0.25 mg of tenecteplase per kg, not exceeding a maximum dose of 25 mg. A single bolus dose should be administered over 5 seconds based on patient weight.</description>
    <arm_group_label>Tenecteplase</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo is being used as the comparator since a thrombolytic is only FDA-approved in the United States for use out to 3 hours, and the standard of care guidelines support use out to 4.5 hours.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient/legally authorized representative has signed the Informed Consent Form&#xD;
&#xD;
          -  Age &gt;= 18 years&#xD;
&#xD;
          -  AIS symptom onset within 4.5 to 24 hours Signs and symptoms consistent with the&#xD;
             diagnosis of an acute anterior circulation ischemic stroke involving occlusion of the&#xD;
             ICA, M1, or M2 vessels&#xD;
&#xD;
          -  Functionally independent (mRS 0-2) prior to stroke onset&#xD;
&#xD;
          -  Baseline NIHSS &gt;=5 and that remains &gt;=5 immediately prior to randomization&#xD;
&#xD;
          -  Neuroimaging: ICA or M1, M2 occlusion (carotid occlusions can be cervical or&#xD;
             intracranial, with or without tandem MCA lesions) by magnetic resonance angiography&#xD;
             (MRA) or computed tomography angiography (CTA) AND target mismatch profile on CT&#xD;
             perfusion or MR perfusion (ischemic core volume &lt;70 mL, mismatch ratio is &gt;=1.8 and&#xD;
             mismatch volume is &gt;= 15 mL)&#xD;
&#xD;
          -  The mismatch volume is determined by FDA-approved imaging software in real time based&#xD;
             on the difference between the ischemic core lesion volume and the Tmax&gt;6s lesion&#xD;
             volume. If both a CT perfusion and a multimodal MRI scan are performed prior to&#xD;
             enrollment, the later of the 2 scans is assessed to determine eligibility. Only an&#xD;
             intracranial MRA is required for patients screened with MRA; cervical MRA is not&#xD;
             required. Cervical and intracranial CTA are typically obtained simultaneously in&#xD;
             patients screened with CTA, but only the intracranial CTA is required for enrollment.&#xD;
&#xD;
        Alternative neuroimaging:&#xD;
&#xD;
          -  If CTA (or MRA) is technically inadequate: Tmax&gt;6s perfusion deficit consistent with&#xD;
             an ICA or M1, M2 occlusion AND target mismatch profile (ischemic core volume &lt;70 mL,&#xD;
             mismatch ratio &gt;= 1.8 and mismatch volume &gt;= 15 mL as determined by RAPID software)&#xD;
&#xD;
          -  If magnetic resonance perfusion (MRP) is technically inadequate: ICA or M1, M2&#xD;
             occlusion (carotid occlusions can be cervical or intracranial; with or without tandem&#xD;
             MCA lesions) by MRA (or CTA, if MRA is technically inadequate and a CTA was performed&#xD;
             within 60 minutes prior to the MRI) AND diffusion-weighted imaging (DWI) lesion volume&#xD;
             &lt;=25 mL for an M1 or ICA occlusion and =&lt;15 mL for an M2 occlusion&#xD;
&#xD;
          -  If CTP is technically inadequate: patient can be screened with MRI and randomized if&#xD;
             neuroimaging criteria are met.&#xD;
&#xD;
          -  Ability to comply with the study protocol, in the investigator's judgment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        General&#xD;
&#xD;
          -  Current participation in another investigational drug or device study&#xD;
&#xD;
          -  Active internal bleeding&#xD;
&#xD;
          -  Known hypersensitivity or allergy to any ingredients of tenecteplase&#xD;
&#xD;
          -  Known bleeding diathesis&#xD;
&#xD;
          -  Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency;&#xD;
             recent oral anticoagulant therapy with INR &gt;1.7&#xD;
&#xD;
          -  Use of one of the new oral anticoagulants within the last 48 hours (dabigatran,&#xD;
             rivaroxaban, apixaban, edoxaban)&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  Intracranial neoplasm (except small meningioma), arteriovenous malformation, or&#xD;
             aneurysm&#xD;
&#xD;
          -  Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS&#xD;
&#xD;
          -  Severe, uncontrolled hypertension (systolic blood pressure &gt;180 mmHg or diastolic&#xD;
             blood pressure &gt; 110 mmHg)&#xD;
&#xD;
          -  For participants with suspected coagulopathy, platelet count must be checked prior to&#xD;
             randomization and participant is excluded if baseline platelet count &lt;100,000/microL&#xD;
&#xD;
          -  Baseline blood glucose &gt;400 mg/dL (22.20 mmol/L)&#xD;
&#xD;
          -  Baseline blood glucose &lt;50 mg/dL needs to be normalized prior to randomization&#xD;
&#xD;
          -  Clot retrieval attempted using a neurothrombectomy device prior to randomization&#xD;
&#xD;
          -  Intracranial or intraspinal surgery or trauma within 2 months&#xD;
&#xD;
          -  Treatment with a thrombolytic within the last 3 months prior to randomization&#xD;
&#xD;
          -  Other serious, advanced, or terminal illness (investigator judgment) with life&#xD;
             expectancy less than 6 months&#xD;
&#xD;
          -  Pre-existing medical, neurological, or psychiatric disease that would confound the&#xD;
             neurological or functional evaluations&#xD;
&#xD;
          -  History of cerebrovascular accident in the last 90 days&#xD;
&#xD;
          -  Presumed septic embolus; suspicion of bacterial endocarditis&#xD;
&#xD;
          -  Any other condition that, in the opinion of the investigator, precludes an&#xD;
             endovascular procedure or poses a significant hazard to the patient if an endovascular&#xD;
             procedure was to be performed&#xD;
&#xD;
        Imaging&#xD;
&#xD;
          -  Unable to undergo a contrast brain perfusion scan with either MRI or CT&#xD;
&#xD;
          -  Extensive early ischemic change (hypodensity) on non-contrast CT estimated to be &gt;1/3&#xD;
             MCA territory, or significant hypodensity outside the Tmax&gt;6s perfusion lesion that&#xD;
             invalidates mismatch criteria (if patient is enrolled based on CT perfusion criteria)&#xD;
&#xD;
          -  Significant mass effect&#xD;
&#xD;
          -  Acute symptomatic arterial occlusions in more than one vascular territory confirmed on&#xD;
             CTA/MRA (e.g., bilateral MCA occlusions, or an MCA and a basilar artery occlusion)&#xD;
&#xD;
          -  Evidence of intracranial tumor (except small meningioma) acute intracranial&#xD;
             hemorrhage, neoplasm, or arteriovenous malformation&#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>University of Alabama at Birmingham</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294-3300</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Banner Desert Medical Center</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - Anaheim (E. La Palma)</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mills-Peninsula Medical Center</name>
      <address>
        <city>Burlingame</city>
        <state>California</state>
        <zip>94010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Muir Health, Concord Medical Center</name>
      <address>
        <city>Concord</city>
        <state>California</state>
        <zip>94520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Davis Hospital</name>
      <address>
        <city>Davis</city>
        <state>California</state>
        <zip>95616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - Fontana</name>
      <address>
        <city>Fontana</city>
        <state>California</state>
        <zip>92335</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adventist Health Glendale</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente South Bay Medical Center</name>
      <address>
        <city>Harbor City</city>
        <state>California</state>
        <zip>90710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSD Medical Center - La Jolla</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90027</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Southern California Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars-Sinai Marina Del Rey Hospital</name>
      <address>
        <city>Marina Del Rey</city>
        <state>California</state>
        <zip>90292</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaiser Permanente - Ontario</name>
      <address>
        <city>Ontario</city>
        <state>California</state>
        <zip>91761</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Roseville Medical Center</name>
      <address>
        <city>Roseville</city>
        <state>California</state>
        <zip>95661</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sutter Medical Group, Neurology</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95816</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCSD - Hillcrest; Hillcrest Medical Center</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CPMC - Van Ness Campus</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CPMC - Davies Campus</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Torrance Memorial Medical Center</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <zip>90505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>John Muir Medical Center-Walnut Creek</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Florida Health at Shands</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Medical Center - Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32207-8202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Medical Center-South</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32258</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jackson Memorial Hospital</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Queen's Medical Center</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96813</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advocate Christ Medical Center</name>
      <address>
        <city>Oak Lawn</city>
        <state>Illinois</state>
        <zip>60453</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advocate Lutheran General Hospital</name>
      <address>
        <city>Park Ridge</city>
        <state>Illinois</state>
        <zip>60068</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Catherine Hospital</name>
      <address>
        <city>East Chicago</city>
        <state>Indiana</state>
        <zip>46312</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Mary Medical Center</name>
      <address>
        <city>Hobart</city>
        <state>Indiana</state>
        <zip>46432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Community Hospital</name>
      <address>
        <city>Munster</city>
        <state>Indiana</state>
        <zip>46321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uni of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Health Corbin</name>
      <address>
        <city>Corbin</city>
        <state>Kentucky</state>
        <zip>40701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Health Lexington</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sinai Hospital of Baltimore</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ of Michigan Medical Ctr</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109-0718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Macomb Hospital - Clinton Township</name>
      <address>
        <city>Clinton Township</city>
        <state>Michigan</state>
        <zip>48038</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McLaren Flint</name>
      <address>
        <city>Flint</city>
        <state>Michigan</state>
        <zip>48532</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spectrum Health Hospitals</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProMedica Monroe Regional Hospital</name>
      <address>
        <city>Monroe</city>
        <state>Michigan</state>
        <zip>48162</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Ridges Hospital</name>
      <address>
        <city>Burnsville</city>
        <state>Minnesota</state>
        <zip>55337</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fairview Southdale</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>U of Minnesota MedCtr Fairview</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Worthington Medical Center</name>
      <address>
        <city>Worthington</city>
        <state>Minnesota</state>
        <zip>56187</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>JFK Neuroscience Institute</name>
      <address>
        <city>Edison</city>
        <state>New Jersey</state>
        <zip>08820</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Health System - Overlook Medical Center</name>
      <address>
        <city>Summit</city>
        <state>New Jersey</state>
        <zip>07901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Capital Health Regional Medical Center</name>
      <address>
        <city>Trenton</city>
        <state>New Jersey</state>
        <zip>08638</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Buffalo General Medical Center</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mission Hospitals Inc</name>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <zip>28803</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guilford Neurologic Research</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Univ of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cleveland Clinic</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riverside Methodist Hospital; Cancer Services</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214-1419</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grant Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Doctors Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43228</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ProMedica Toledo Hospital</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension St. John</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adventist Health Portland</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Saint Vincent's Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC East Hospital</name>
      <address>
        <city>Monroeville</city>
        <state>Pennsylvania</state>
        <zip>15146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Penn Presbyterian Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uni of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pennsylvania Hospital</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Mercy</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Passavant Hospital</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanford Neurology Clinic</name>
      <address>
        <city>Sioux Falls</city>
        <state>South Dakota</state>
        <zip>57104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chattanooga Center for Neurologic Research</name>
      <address>
        <city>Chattanooga</city>
        <state>Tennessee</state>
        <zip>37404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Thomas Rutherford Hospital</name>
      <address>
        <city>Murfreesboro</city>
        <state>Tennessee</state>
        <zip>37129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Thomas Health</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Thomas Midtown Hospital</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dell Seton Medical center at the University of Texas</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seton Medical Center Austin</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Baptist Medical Center-Brownsville</name>
      <address>
        <city>Brownsville</city>
        <state>Texas</state>
        <zip>78520</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor University Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Valley Baptist Medical Center</name>
      <address>
        <city>Harlingen</city>
        <state>Texas</state>
        <zip>78550</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas at Houston; Neurology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Seton Hays</name>
      <address>
        <city>Kyle</city>
        <state>Texas</state>
        <zip>78640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ascension Seton Williamson</name>
      <address>
        <city>Round Rock</city>
        <state>Texas</state>
        <zip>78665</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Health Science Center at San Antonio</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22906</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Uni of Alberta</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2G3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hamilton General Hospital; Pharmacy</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8L 2X2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montreal Neurological Inst; Clinical Research Unit</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H3A 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 24, 2018</study_first_posted>
  <last_update_submitted>April 27, 2023</last_update_submitted>
  <last_update_submitted_qc>April 27, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenecteplase</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03785678
org study id: ML40787
nct id: NCT03785678
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will evaluate the efficacy and safety of tenecteplase compared with placebo in
      participants with acute ischemic stroke (AIS).

      All participants will receive standard-of-care therapy according to AmericanHeart
      Association/American Stroke Association clinical guidelines (2018). To determine eligibility
      for randomization, all participants will undergo multimodal CT or MRI at baseline. Only
      participants with a vessel occlusion (ICA or MCA M1/M2) and penumbral tissue will be
      randomized. The primary analysis is to compare the efficacy of tenecteplase versus placebo in
      all participants at Day 90.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Ordinal modified Rankin scale (mRS) score
time frame: Day 90
description: The Efficacy of Tenecteplase compared to placebo is evaluated in terms of Ordinal mRS score at day 90.
measure: Proportion of patients with functional independence
time frame: Day 90
description: The efficacy of Tenecteplase is evaluated in terms of proportion of patients with functional independence, defined as an mRS of 0-2, at Day 90
measure: Proportion of patients with angiographic reperfusion
time frame: Day 1
description: The efficacy of Tenecteplase is evaluated in terms of proportion of patients with angiographic reperfusion at completion of angiographic procedure (endovascular patients only).
measure: Median NIHSS score
time frame: Day 90
description: The efficacy of Tenecteplase is evaluted in terms of Median NIHSS score at Day 90.
measure: Proportion of patients with a Barthel Index (BI) score >=95
time frame: Day 90
description: The efficacy of Tenecteplase is evaluated in terms of Proportion of patients with a BI score >=95 at Day 90.
measure: Proportion of patients with good recovery based on the Glasgow Outcome Scale (GOS) at Day 90
time frame: Day 90
description: The efficacy of Tenecteplase is evaluated in terms of the proportion of patients with good recovery based on the GOS at Day 90.
measure: Proportion of patients with reperfusion at 24 hours post-randomization
time frame: Day 2
description: The efficacy of Tenecteplase is evaluated in terms of proportion of patients with reperfusion at 24 hours post-randomization, defined as >90% reduction in Tmax>6s lesion volume
measure: Proportion of patients with recanalization at 24 hours post-randomization
time frame: Day 2
description: The efficacy of Tenecteplase is evaluated in terms of proportion of patients with recanalization at 24 hours post-randomization, defined as complete or partial recanalization on CT angiography (CTA)/magnetic resonance angiography (MRA).
measure: Number of patients with symptomatic intracranial hemorrhage (sICH a)
time frame: Day 2
description: The safety profile of Tenecteplase is evaluated in terms of number of patients with sICH within 36 hours
measure: Incidence and severity of adverse events
time frame: From baseline up to day 90
description: The safety profile of Tenecteplase is evaluated in terms of incidence and severity of adverse events.
measure: Mortality rate up to Day 30 and Day 90
time frame: Day 30 and Day 90
description: The safety profile of Tenecteplase is evaluated in terms of mortality rate up to Day 30 and Day 90
measure: Proportion of patients with parenchymal hematoma type 2 (PH2) at the 72-96 hour visit
time frame: Day 3
description: The safety profile of Tenecteplase is evaluated in terms of proportion of patients with PH2 at the 72-96 hour visit
arm group label: Tenecteplase
arm group type: Experimental
description: Patients in this arm will receive Tenecteplase (0.25 mg/kg, maximum 25 mg) administered as a single bolus injection over 5 seconds.
arm group label: Placebo
arm group type: Placebo Comparator
description: Patients in this arm will receive placebo administered as a single bolus injection over 5 seconds.
intervention type: Biological
intervention name: Tenecteplase
description: The investigational medicinal product (IMP) for this study is tenecteplase. The recommended total dose for this study is weight-based with 0.25 mg of tenecteplase per kg, not exceeding a maximum dose of 25 mg. A single bolus dose should be administered over 5 seconds based on patient weight.
arm group label: Tenecteplase
intervention type: Other
intervention name: Placebo
description: Placebo is being used as the comparator since a thrombolytic is only FDA-approved in the United States for use out to 3 hours, and the standard of care guidelines support use out to 4.5 hours.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Tenecteplase