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/NCT05983757</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY23030032</org_study_id>
      <nct_id>NCT05983757</nct_id>
    </id_info>
    <brief_title>Combined Thrombectomy for Distal MediUm Vessel Occlusion StroKe</brief_title>
    <acronym>DUSK</acronym>
    <official_title>A Phase III, Randomized, Multicenter, Investigational, Open Label Clinical Trial That Will Examine Whether Treatment With Endovascular Thrombectomy is Superior to Standard Medical Therapy Alone in Patients Who Suffer a Distal Medium Vessel Occlusion Ischemic Strokes.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Raul Nogueira</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Stryker Neurovascular</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Brainstorme Imaging Core Lab Inc</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Berry Consultants</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Pittsburgh</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        A phase III, randomized, multi-center, investigational, open label clinical trial that will&#xD;
        examine whether treatment with endovascular thrombectomy is superior to standard medical&#xD;
        therapy alone in patients who suffer a Distal Medium Vessel Occlusion Ischemic Stroke within&#xD;
        12 hours from time last seen well&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        DUSK is a Phase-3, prospective, multicenter, investigational, randomized, controlled,&#xD;
        open-label study with blinded endpoint evaluation (PROBE design) and an adaptive design with&#xD;
        population enrichment. The randomization employs a 1:1 ratio of endovascular thrombectomy&#xD;
        (EVT) versus standard medical management (SMM) in patients who suffer a distal medium vessel&#xD;
        occlusion (DMVO) stroke within 12 hours from time last seen well (TLSW) and have evidence of&#xD;
        salvageable brain tissue on perfusion imaging. Randomization will be done under a&#xD;
        minimization process using age (≤67 vs. &gt;67 years), baseline NIHSS (≤12 vs. &gt;12), use of IV&#xD;
        thrombolysis (none vs. within 120 minutes from randomization vs. &gt; 120 minutes from&#xD;
        randomization), site of occlusion (M2 vs. M3 vs. ACA vs. PCA), baseline infarct volume (≤15mL&#xD;
        vs. &gt;15-30mL vs. &gt;30-50mL), perfusion mismatch volume (≤15mL vs. &gt;15-30mL vs. &gt;30-50mL),&#xD;
        therapeutic window (0-4.5 vs. 4.5-8 or &gt;9-12 hours after TLKW), and participating site. The&#xD;
        candidate enriched populations that the trial considers are based on use of intravenous&#xD;
        thrombolysis (none vs. within 120 minutes from randomization vs. &gt; 120 minutes from&#xD;
        randomization), TLKW to randomization (0-6 vs. 6-12 hours) and mismatch volumes as measured&#xD;
        using absolute mismatch (defined as Tmax&gt;6 sec - DWI lesion on MRI or Tmax&gt;6 sec -rCBF&lt;30%&#xD;
        lesion on CTP) (&gt;40 cc vs. &gt;30cc vs. &gt;20cc vs. &gt;10cc). The primary endpoint will be a&#xD;
        categorical shift across all levels on the modified Rankin Scale (mRS) at 90-days&#xD;
        post-randomization. The hypothesis is that EVT will lead to an improved clinical outcome at&#xD;
        90 days. Interim analysis will be performed after the primary endpoint is available for a&#xD;
        total of 386 randomized patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">December 2026</completion_date>
    <primary_completion_date type="Anticipated">June 2026</primary_completion_date>
    <phase>N/A</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>
      <intervention_model_description>The randomization employs a 1:1 ratio of endovascular thrombectomy (EVT) with the use of Trevo NXT ProVue Retrievers, AXS Vecta 46 Intermediate Catheter and AXS Catalyst 5 Distal Access Catheter, versus standard medical management (SMM) in patients who suffer a distal medium vessel occlusion (DMVO) stroke within 12 hours from time last seen well (TLSW) and have evidence of salvageable brain tissue on perfusion imaging. Randomization will be done under a minimization process using age (≤67 vs. &gt;67 years), baseline NIHSS (≤12 vs. &gt;12), use of IV thrombolysis (none vs. within 120 minutes from randomization vs. &gt; 120 minutes from randomization), site of occlusion (M2 vs. M3 vs. ACA vs. PCA), baseline infarct volume (≤15mL vs. &gt;15-30mL vs. &gt;30-50mL), perfusion mismatch volume (≤15mL vs. &gt;15-30mL vs. &gt;30-50mL), therapeutic window (0-4.5 vs. 4.5-8 or &gt;9-12 hours after TLKW), and participating site.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>One investigator or designee will remain blinded at each site to perform primary outcome assessment at Day 30 and Day 90.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Shift in distribution of all levels of the 90-day modified Rankin Scale with levels 5-6 combined (mRS; 0, 1, 2, 3, 4, 5-6) as assessed by structured assessment</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>Modified Rankin Scale measurement (mRS): 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Shift in distribution of the 90-day mRS (0;1;2;3;4;5;6) as assessed by structured assessment</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>Modified Rankin Scale measurement (mRS)0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of Independent Outcome defined as mRS ≤2 and/ or equal to Baseline mRS at 90 days</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>Independant outcome: 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of Excellent Outcome defined as mRS ≤1 and/ or equal to Baseline mRS at 90 days</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>Excellent outcome: 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rates of Good Functional Outcomes adjusted for the baseline mRS and stroke severity (NIHSS) according to the modified Rankin Scale scores at 90 days as following:</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>NIHSS and mRS scores MRS: 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead NIHSS: 0=no stroke symptoms, 1-4=minor stroke, 5-15 moderate stroke, 16-20 moderate to sever stroke, 21-42- severe stroke.&#xD;
  If NIHSS &lt;10 and Baseline mRS 0 or 1: 90-day mRS ≤1&#xD;
  If NIHSS &lt;10 and Baseline mRS 2: 90-day mRS ≤2&#xD;
  If NIHSS ≥10 and Baseline mRS 0 or 1: 90-day mRS ≤2&#xD;
  If NIHSS ≥10 and Baseline mRS 2: 90-day mRS ≤3</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EVT arm only: Final reperfusion grades according to the extended Thrombolysis in Cerebral Infarction (eTICI) scale and the rates of First Pass Effect (eTICI ≥2c) and Modified First Pass Effect (eTICI ≥2b50)</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>Reprofusion grades :TICI scores:grade 0: no perfusion noted (0% reperfusion) grade 1: reduction in thrombus but without any resultant filling of distal arterial branches grade 2 grade 2a: reperfusion of 1-49% of the territory grade 2b50: reperfusion of 50-66% of the territory grade 2b67: reperfusion of 67-89% of the territory grade 2c: extensive reperfusion of 90-99% of the territory grade 3: complete or full reperfusion (100% reperfusion).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EVT arm only: Final reperfusion grades according to the rates of First Pass Effect (eTICI ≥2c)</measure>
      <time_frame>90-Day follow up</time_frame>
      <description>Reprofusion grades :TICI scores:grade 0: no perfusion noted (0% reperfusion) grade 1: reduction in thrombus but without any resultant filling of distal arterial branches grade 2 grade 2a: reperfusion of 1-49% of the territory grade 2b50: reperfusion of 50-66% of the territory grade 2b67: reperfusion of 67-89% of the territory grade 2c: extensive reperfusion of 90-99% of the territory grade 3: complete or full reperfusion (100% reperfusion).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>EVT arm only: Final reperfusion grades according to the Modified First Pass Effect (eTICI ≥2b50)</measure>
      <time_frame>90 day follow up</time_frame>
      <description>Reprofusion grades :TICI scores:grade 0: no perfusion noted (0% reperfusion) grade 1: reduction in thrombus but without any resultant filling of distal arterial branches grade 2 grade 2a: reperfusion of 1-49% of the territory grade 2b50: reperfusion of 50-66% of the territory grade 2b67: reperfusion of 67-89% of the territory grade 2c: extensive reperfusion of 90-99% of the territory grade 3: complete or full reperfusion (100% reperfusion).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS) at 90 days</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>utility weighted mRS 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Final infarct volume (FIV) (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 24 hours (-2/+12 hours)</measure>
      <time_frame>24 hours (-2hours /+12 hours)</time_frame>
      <description>Infarct volume at 24 hours will be measured on CT or MRI.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Final infarct growth (FIV - baseline infarct on CTP or DWI)</measure>
      <time_frame>24 hours (-2 hours/+12 hours)</time_frame>
      <description>Infarct volume at 24 hours will be measured on CT or MRI, growth of infarct from baseline to 24 hours will be captured.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available)</measure>
      <time_frame>3-5 days</time_frame>
      <description>Infarct volume at 3-5 days will be measured on CT or MRI.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Final infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available)</measure>
      <time_frame>3 to 5 days</time_frame>
      <description>Infarct volume at 3-5 days will be measured on CT or MRI, growth of infarct will be compared to baseline.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Clinical improvement at 24 hours calculated as the difference between 24-hour and baseline NIHSS score</measure>
      <time_frame>24 hours</time_frame>
      <description>NIHSS score at 24hours :NIHSS: 0=no stroke symptoms, 1-4=minor stroke, 5-15 moderate stroke, 16-20 moderate to sever stroke, 21-42- severe stroke.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cost effectiveness analysis of endovascular thrombectomy vs standard medical therapy</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>Assessment of costs from the time of randomization to the 90 day follow up. This includes Costs of hospitalization, institutional living and outpatient care will be assessed and compared for each arm.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Brain tissue reperfusion evaluated by CT or MRI perfusion at 24 hours in both treatment groups (if available)</measure>
      <time_frame>24 hours</time_frame>
      <description>CT or MRI results at 24 hours</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Vessel patency evaluated by CTA or MRA perfusion at 24 hours in both treatment groups (if available)</measure>
      <time_frame>24 hours</time_frame>
      <description>CTA or MRA perfusion results at 24 hours</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient reported outcomes (EQ-5D)</measure>
      <time_frame>90-day follow-up</time_frame>
      <description>Questionnaires assessed by blinded assessor at 90 days. EQ-5D measures mobility, self care, usual activities, pain and anxiety, overall heath is measured on a scale of 0 (worst health state) to 100 best health state.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient reported outcomes (PROMIS Global-10)</measure>
      <time_frame>90 day follow up</time_frame>
      <description>Questionnaires assessed by blinded assessor at 90 days. Promise Global Health measures current health status on a scale of 1=poor, 2=fair, 3=good, 4=very good, 5=excellent. The scale is from 1-5 with 1 being the poorest health outcome and 5 the best.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient reported outcomes (PROMIS Fatigue)</measure>
      <time_frame>90 day follow up</time_frame>
      <description>Questionnaires assessed by blinded assessor at 90 days. Promise Fatigue will measure degree of fatigue on a scale of 1=not at all, 2=a little bit, 3=somewhat, 4= quite a bit, 5=very much. The scale is from 1-5 with 1 being the least fatigued and 5 the greatest feeling of fatigue.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient reported outcomes ( IADL)</measure>
      <time_frame>90 day follow up</time_frame>
      <description>Questionnaires assessed by blinded assessor at 90 days. IADL measures the ability to use a telephone, shop prepare food, do housekeeping, laundry, mode of transportation, medications and handle finances. The subject will answer the questions and answer as for how they are able to accomplish their ADLs.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Patient reported outcomes ( MoCa)</measure>
      <time_frame>90 day follow up</time_frame>
      <description>Questionnaires assessed by blinded assessor at 90 days. MoCa measures the patient's ability to draw(visuospatial), name items, memory, attention, language, and abstraction. There are several questions that the subject will answer for each category.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All cause mortality</measure>
      <time_frame>90 day follow up</time_frame>
      <description>All-cause mortality within 90 days</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mortality due to stroke</measure>
      <time_frame>90 day follow up</time_frame>
      <description>Mortality within 90 days due to index stroke</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial hemorrhage</measure>
      <time_frame>90 day follow up</time_frame>
      <description>Symptomatic intracranial hemorrhage (SICH) defined as per the modified SITS-MOST definition:local or remote parenchymal hemorrhage type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage on the post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 h (-2/+12), or leading to death that the CEC/DSMB judges is causative of the deterioration. (https://www.sitsinternational.org/research/studies/sits-most-ii/)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Intracranial hemorrhage</measure>
      <time_frame>24 hours (-2 hours /+12 hours)</time_frame>
      <description>The incidence of any intracranial hemorrhage measured at 24 (-2/+12) hours as graded by the central core-lab using the Heidelberg classification criteria.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Procedure-related vessel perforation.</measure>
      <time_frame>24 hours (-2 hours /+12 hours)</time_frame>
      <description>Perforation of the artery related to the procedure.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Procedure-related vessel dissection</measure>
      <time_frame>24 hours (-2 hours/+12 hours)</time_frame>
      <description>Dissection of an artery related to the procedure.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Embolization to a new territory during mechanical thrombectomy (MT) procedure</measure>
      <time_frame>24 hours (-2 hours/+12hours)</time_frame>
      <description>New emboli to a different area of the brain during the MR procedure.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Significant extracranial hemorrhage (e.g., access site, retroperitoneal hematoma) requiring blood transfusion and/or surgical intervention.</measure>
      <time_frame>24 hours (-2 hours/+12 hours)</time_frame>
      <description>Hemorrhage in other areas besides the brain such as the arterial access site or retroperitoneum.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">564</enrollment>
    <condition>Ischemic Stroke</condition>
    <arm_group>
      <arm_group_label>Standard of Care Treatment</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Standard medical management in patients who suffer a distal medium vessel occlusion</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Endovascular Thrombectomy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Endovascular thrombectomy in patients who suffer a distal medium vessel occlusion.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Experimental: endovascular thrombectomy in patients who suffer a distal medium vessel occlusion</intervention_name>
      <description>The AXS Catalyst Distal Access Catheter is indicated for use in facilitating the insertion and guidance of appropriately sized interventional devices into a selected blood vessel in the peripheral and neurovascular systems, and is also indicated for use as a conduit for retrieval devices.&#xD;
  The AXS Vecta Intermediate Catheter, as part of the AXS Vecta Aspiration System, is indicated in the revascularization of patients with acute ischemic stroke. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who failed IV t-PA therapy are candidates for treatment.&#xD;
  The Trevo® Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA).</description>
      <arm_group_label>Endovascular Thrombectomy</arm_group_label>
      <other_name>AXS Vecta 46</other_name>
      <other_name>AXS CAT 5</other_name>
      <other_name>NXT ProVue Retriever</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Standard medical management</intervention_name>
      <description>All subjects should receive the best standard medical therapy based on current AHA guidelines. Subjects randomized to standard medical management (SMM) will receive standard medical therapy only based on the guidelines. All subjects are expected to be admitted to hospital as part of routine best guideline-based care and treated on a stroke unit or neurointensive care unit or equivalent.</description>
      <arm_group_label>Standard of Care Treatment</arm_group_label>
      <other_name>Active Comparator</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥18 years (no upper age limit)&#xD;
  &#xD;
            2. Acute ischemic stroke where patient is ineligible for or has failed* IV thrombolytic&#xD;
               treatment and is ineligible for endovascular treatment under best guideline-based care&#xD;
               due to absence of proximal arterial occlusion (e.g. intracranial ICA, MCA-M1 and&#xD;
               co-dominant or dominant M2** segments, and vertebrobasilar arteries).***&#xD;
  &#xD;
               * IV thrombolytic treatment failure is defined by persistent disabling neurological&#xD;
               deficits beyond 60 minutes of completion of thrombolytic infusion in the presence of&#xD;
               imaging findings consistent with DMVO.&#xD;
  &#xD;
               **Dominant M2 segment is defined is a division supplying &gt;50% of the MCA territory vs&#xD;
               co-dominant supplying 50% of the MCA territory vs non-dominant supplying &lt;50% of the&#xD;
               MCA territory.&#xD;
  &#xD;
               ***No procedures or tests required by the protocol will delay fastest possible&#xD;
               delivery of thrombolytic therapy to potentially eligible subjects.&#xD;
  &#xD;
            3. Evidence of a primary (e.g. not secondary to EVT of proximal vessel occlusion) distal&#xD;
               medium vascular occlusion defined as occlusion of the non-dominant M2 segment or M3&#xD;
               segment of the MCA, the ACA (A1, A2, or A3 segments), or the PCA (P1, P2 or P3&#xD;
               segments) resulting in significant clinical deficits and expected to be treatable by&#xD;
               endovascular thrombectomy. Non dominant M2 segment vessel diameter should not exceed&#xD;
               2.5mm.&#xD;
  &#xD;
            4. No significant pre-stroke functional disability (mRS ≤2)&#xD;
  &#xD;
            5. Evidence of a disabling stroke defined as follows:&#xD;
  &#xD;
                 1. Baseline National Institutes of Health Stroke Scale (NIHSS) score &gt;5 at the time&#xD;
                    of randomization.&#xD;
  &#xD;
                 2. NIHSS 3-5 with disabling deficit including significant aphasia, neglect,&#xD;
                    hemianopsia, or hemiparesis/ loss of hand or leg function as established by the&#xD;
                    treating team in context of the patient's life.&#xD;
  &#xD;
            6. The presence of a Target Mismatch defined as:&#xD;
  &#xD;
                 1. Ischemic Core &lt; 50cc (defined on NCCT/CTP* or DWI-MRI)&#xD;
  &#xD;
                    *Visual or automatedly detected hypodensity on NCCT should be used to exclude or&#xD;
                    include patients if the investigator believes that their assessment is more&#xD;
                    reliable than the CTP volume in any particular case.&#xD;
  &#xD;
                 2. Mismatch Volume (TMax &gt;6sec lesion - Core volume lesion) &gt;10cc&#xD;
  &#xD;
                 3. Mismatch Ratio &gt;1.4&#xD;
  &#xD;
            7. Patient treatable within 12 hours of symptom onset. Symptoms onset is defined as the&#xD;
               point in time the patient was last seen well (at baseline). Treatment start is defined&#xD;
               as the time of arterial puncture.&#xD;
  &#xD;
            8. Informed consent obtained from patient or acceptable patient surrogate&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Any sign of intracranial hemorrhage on baseline CT/MR (SDH/SAH/ICH).&#xD;
  &#xD;
            2. Rapidly improving symptoms, particularly if in the judgment of the managing clinician&#xD;
               that the improvement is likely to result in the patient having no residual disabling&#xD;
               deficits and an NIHSS score of &lt;5 at randomization.&#xD;
  &#xD;
            3. Significant ischemic changes in a territory other than the occluded site that in the&#xD;
               opinion of the investigator could reduce the benefit of endovascular treatment.&#xD;
  &#xD;
            4. Contra indication to imaging with MR or CT with contrast agents.&#xD;
  &#xD;
            5. Infarct core &gt;1/3 occluded territory (MCA, ACA, or PCA) qualitatively or &gt;50 mL&#xD;
               quantitatively (determined by NCCT, CTP or DWI).&#xD;
  &#xD;
            6. Any terminal illness such that patient would not be expected to survive more than 1&#xD;
               year.&#xD;
  &#xD;
            7. Recent past history or clinical presentation of ICH, subarachnoid hemorrhage (SAH),&#xD;
               arterio-venous (AV) malformation, aneurysm, or cerebral neoplasm other than&#xD;
               meningioma.&#xD;
  &#xD;
            8. Any imaging findings suggestive of futile recanalization in the judgment of the local&#xD;
               investigator.&#xD;
  &#xD;
            9. Premorbid disability (mRS ≥3).&#xD;
  &#xD;
           10. Inability to initiate endovascular treatment within 12 hours of last known well.&#xD;
  &#xD;
           11. Seizures at stroke onset if it precludes obtaining an accurate baseline NIHSS.&#xD;
  &#xD;
           12. Baseline blood glucose of &lt;50 mg/dL (2.78 mmol) or &gt;400 mg/dL (22.20 mmol).&#xD;
  &#xD;
           13. Known history of hereditary or acquired hemorrhagic diathesis and/or platelet count&#xD;
               &lt;100,000/uL.&#xD;
  &#xD;
           14. Known renal failure as defined as serum creatinine levels &gt; 3.0 mg/dL.&#xD;
  &#xD;
           15. Presumed septic embolus or suspicion of bacterial endocarditis.&#xD;
  &#xD;
           16. Any other condition that, in the opinion of the investigator, precludes an&#xD;
               endovascular procedure or poses a significant hazard to the subject if an endovascular&#xD;
               procedure was performed.&#xD;
  &#xD;
           17. History of drug or alcohol use or dependence that, in the opinion of the site&#xD;
               investigator, would interfere with adherence to study requirements.&#xD;
  &#xD;
           18. Subjects with occlusions in multiple vascular territories (e.g., bilateral or&#xD;
               multi-territorial anterior circulation, or anterior/posterior circulation)&#xD;
  &#xD;
           19. Subject participating in a study involving an investigational drug or device that&#xD;
               would impact this study&#xD;
  &#xD;
           20. Known pregnancy&#xD;
  &#xD;
           21. Prisoner or incarceration&#xD;
  &#xD;
           22. Known acute symptomatic COVID-19 infection&#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_official>
      <last_name>Raul G Nogueira, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Pittsburgh</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Denise McCarthy, MPPM RN</last_name>
      <phone>1-878-261-6015</phone>
      <email>mccarthydj@upmc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Emma Gyurisin, MPH</last_name>
      <phone>4126779128</phone>
      <email>gyurisinek2@upmc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>University of Pittsburgh</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15213</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Denise McCarthy, MPPM RN</last_name>
        <phone>878-261-6015</phone>
        <email>mccarthydj@upmc.edu</email>
      </contact>
      <investigator>
        <last_name>Nirav Bhatt, MD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <reference>
      <citation>Ospel JM, Goyal M. A review of endovascular treatment for medium vessel occlusion stroke. J Neurointerv Surg. 2021 Jul;13(7):623-630. doi: 10.1136/neurintsurg-2021-017321. Epub 2021 Feb 26.</citation>
      <PMID>33637570</PMID>
    </reference>
    <reference>
      <citation>Saver JL, Chapot R, Agid R, Hassan A, Jadhav AP, Liebeskind DS, Lobotesis K, Meila D, Meyer L, Raphaeli G, Gupta R; Distal Thrombectomy Summit Group*dagger. Thrombectomy for Distal, Medium Vessel Occlusions: A Consensus Statement on Present Knowledge and Promising Directions. Stroke. 2020 Sep;51(9):2872-2884. doi: 10.1161/STROKEAHA.120.028956. Epub 2020 Aug 6. No abstract available. Erratum In: Stroke. 2020 Oct;51(10):e296.</citation>
      <PMID>32757757</PMID>
    </reference>
    <reference>
      <citation>Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30. Erratum In: Stroke. 2019 Dec;50(12):e440-e441.</citation>
      <PMID>31662037</PMID>
    </reference>
    <reference>
      <citation>Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, Schellinger PD, Toni D, de Vries J, White P, Fiehler J. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE). Eur Stroke J. 2019 Mar;4(1):6-12. doi: 10.1177/2396987319832140. Epub 2019 Feb 26.</citation>
      <PMID>31165090</PMID>
    </reference>
    <reference>
      <citation>Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, Levi CR, Hsu C, Kleinig TJ, Fatar M, Leys D, Molina C, Wijeratne T, Curtze S, Dewey HM, Barber PA, Butcher KS, De Silva DA, Bladin CF, Yassi N, Pfaff JAR, Sharma G, Bivard A, Desmond PM, Schwab S, Schellinger PD, Yan B, Mitchell PJ, Serena J, Toni D, Thijs V, Hacke W, Davis SM, Donnan GA; EXTEND, ECASS-4, and EPITHET Investigators. Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet. 2019 Jul 13;394(10193):139-147. doi: 10.1016/S0140-6736(19)31053-0. Epub 2019 May 22. Erratum In: Lancet. 2020 Jun 20;395(10241):1906.</citation>
      <PMID>31128925</PMID>
    </reference>
    <reference>
      <citation>Ospel JM, Menon BK, Demchuk AM, Almekhlafi MA, Kashani N, Mayank A, Fainardi E, Rubiera M, Khaw A, Shankar JJ, Dowlatshahi D, Puig J, Sohn SI, Ahn SH, Poppe A, Calleja A, Hill MD, Goyal M. Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment. Stroke. 2020 Nov;51(11):3232-3240. doi: 10.1161/STROKEAHA.120.030227. Epub 2020 Oct 19.</citation>
      <PMID>33070714</PMID>
    </reference>
    <reference>
      <citation>Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.</citation>
      <PMID>26898852</PMID>
    </reference>
    <reference>
      <citation>Menon BK, Hill MD, Davalos A, Roos YBWEM, Campbell BCV, Dippel DWJ, Guillemin F, Saver JL, van der Lugt A, Demchuk AM, Muir K, Brown S, Jovin T, Mitchell P, White P, Bracard S, Goyal M. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration. J Neurointerv Surg. 2019 Nov;11(11):1065-1069. doi: 10.1136/neurintsurg-2018-014678. Epub 2019 Apr 11.</citation>
      <PMID>30975736</PMID>
    </reference>
    <reference>
      <citation>Haussen DC, Lima A, Nogueira RG. The Trevo XP 3x20 mm retriever ('Baby Trevo') for the treatment of distal intracranial occlusions. J Neurointerv Surg. 2016 Mar;8(3):295-9. doi: 10.1136/neurintsurg-2014-011613. Epub 2015 May 6.</citation>
      <PMID>25948592</PMID>
    </reference>
    <reference>
      <citation>Haussen DC, Al-Bayati AR, Eby B, Ravindran K, Rodrigues GM, Frankel MR, Nogueira RG. Blind exchange with mini-pinning technique for distal occlusion thrombectomy. J Neurointerv Surg. 2020 Apr;12(4):392-395. doi: 10.1136/neurintsurg-2019-015205. Epub 2019 Aug 31.</citation>
      <PMID>31473647</PMID>
    </reference>
    <reference>
      <citation>Perez-Garcia C, Moreu M, Rosati S, Simal P, Egido JA, Gomez-Escalonilla C, Arrazola J. Mechanical Thrombectomy in Medium Vessel Occlusions: Blind Exchange With Mini-Pinning Technique Versus Mini Stent Retriever Alone. Stroke. 2020 Nov;51(11):3224-3231. doi: 10.1161/STROKEAHA.120.030815. Epub 2020 Oct 19.</citation>
      <PMID>33070712</PMID>
    </reference>
    <reference>
      <citation>Grossberg JA, Rebello LC, Haussen DC, Bouslama M, Bowen M, Barreira CM, Belagaje SR, Frankel MR, Nogueira RG. Beyond Large Vessel Occlusion Strokes: Distal Occlusion Thrombectomy. Stroke. 2018 Jul;49(7):1662-1668. doi: 10.1161/STROKEAHA.118.020567. Epub 2018 Jun 18. Erratum In: Stroke. 2018 Sep;49(9):e298.</citation>
      <PMID>29915125</PMID>
    </reference>
    <reference>
      <citation>Nogueira RG, Mohammaden MH, Haussen DC, Budzik RF, Gupta R, Krajina A, English JD, Malek AR, Sarraj A, Narata AP, Taqi MA, Frankel MR, Miller TR, Grobelny T, Baxter BW, Bartolini BM, Jenkins P, Estrade L, Liebeskind D, Veznedaroglu E; Trevo Registry Investigators. Endovascular therapy in the distal neurovascular territory: results of a large prospective registry. J Neurointerv Surg. 2021 Nov;13(11):979-984. doi: 10.1136/neurintsurg-2020-016851. Epub 2020 Dec 15.</citation>
      <PMID>33323503</PMID>
    </reference>
    <reference>
      <citation>Goyal M, Ospel JM, Menon BK, Hill MD. MeVO: the next frontier? J Neurointerv Surg. 2020 Jun;12(6):545-547. doi: 10.1136/neurintsurg-2020-015807. Epub 2020 Feb 14. No abstract available.</citation>
      <PMID>32060151</PMID>
    </reference>
    <reference>
      <citation>Seners P, Turc G, Maier B, Mas JL, Oppenheim C, Baron JC. Incidence and Predictors of Early Recanalization After Intravenous Thrombolysis: A Systematic Review and Meta-Analysis. Stroke. 2016 Sep;47(9):2409-12. doi: 10.1161/STROKEAHA.116.014181. Epub 2016 Jul 26.</citation>
      <PMID>27462117</PMID>
    </reference>
    <reference>
      <citation>Menon BK, Al-Ajlan FS, Najm M, Puig J, Castellanos M, Dowlatshahi D, Calleja A, Sohn SI, Ahn SH, Poppe A, Mikulik R, Asdaghi N, Field TS, Jin A, Asil T, Boulanger JM, Smith EE, Coutts SB, Barber PA, Bal S, Subramanian S, Mishra S, Trivedi A, Dey S, Eesa M, Sajobi T, Goyal M, Hill MD, Demchuk AM; INTERRSeCT Study Investigators. Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke. JAMA. 2018 Sep 11;320(10):1017-1026. doi: 10.1001/jama.2018.12498.</citation>
      <PMID>30208455</PMID>
    </reference>
    <reference>
      <citation>Tian H, Parsons MW, Levi CR, Lin L, Aviv RI, Spratt NJ, Butcher KS, Lou M, Kleinig TJ, Bivard A. Influence of occlusion site and baseline ischemic core on outcome in patients with ischemic stroke. Neurology. 2019 Jun 4;92(23):e2626-e2643. doi: 10.1212/WNL.0000000000007553. Epub 2019 May 1.</citation>
      <PMID>31043475</PMID>
    </reference>
    <reference>
      <citation>Lima FO, Furie KL, Silva GS, Lev MH, Camargo EC, Singhal AB, Harris GJ, Halpern EF, Koroshetz WJ, Smith WS, Nogueira RG. Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography. JAMA Neurol. 2014 Feb;71(2):151-7. doi: 10.1001/jamaneurol.2013.5007.</citation>
      <PMID>24323077</PMID>
    </reference>
    <reference>
      <citation>Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, Cheripelli B, Cho TH, Fazekas F, Fiehler J, Ford I, Galinovic I, Gellissen S, Golsari A, Gregori J, Gunther M, Guibernau J, Hausler KG, Hennerici M, Kemmling A, Marstrand J, Modrau B, Neeb L, Perez de la Ossa N, Puig J, Ringleb P, Roy P, Scheel E, Schonewille W, Serena J, Sunaert S, Villringer K, Wouters A, Thijs V, Ebinger M, Endres M, Fiebach JB, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Gerloff C; WAKE-UP Investigators. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018 Aug 16;379(7):611-622. doi: 10.1056/NEJMoa1804355. Epub 2018 May 16.</citation>
      <PMID>29766770</PMID>
    </reference>
    <reference>
      <citation>Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, Kleinig TJ, Wijeratne T, Curtze S, Dewey HM, Miteff F, Tsai CH, Lee JT, Phan TG, Mahant N, Sun MC, Krause M, Sturm J, Grimley R, Chen CH, Hu CJ, Wong AA, Field D, Sun Y, Barber PA, Sabet A, Jannes J, Jeng JS, Clissold B, Markus R, Lin CH, Lien LM, Bladin CF, Christensen S, Yassi N, Sharma G, Bivard A, Desmond PM, Yan B, Mitchell PJ, Thijs V, Carey L, Meretoja A, Davis SM, Donnan GA; EXTEND Investigators. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019 May 9;380(19):1795-1803. doi: 10.1056/NEJMoa1813046. Erratum In: N Engl J Med. 2021 Apr 1;384(13):1278.</citation>
      <PMID>31067369</PMID>
    </reference>
    <reference>
      <citation>Thomalla G, Boutitie F, Ma H, Koga M, Ringleb P, Schwamm LH, Wu O, Bendszus M, Bladin CF, Campbell BCV, Cheng B, Churilov L, Ebinger M, Endres M, Fiebach JB, Fukuda-Doi M, Inoue M, Kleinig TJ, Latour LL, Lemmens R, Levi CR, Leys D, Miwa K, Molina CA, Muir KW, Nighoghossian N, Parsons MW, Pedraza S, Schellinger PD, Schwab S, Simonsen CZ, Song SS, Thijs V, Toni D, Hsu CY, Wahlgren N, Yamamoto H, Yassi N, Yoshimura S, Warach S, Hacke W, Toyoda K, Donnan GA, Davis SM, Gerloff C; Evaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data. Lancet. 2020 Nov 14;396(10262):1574-1584. doi: 10.1016/S0140-6736(20)32163-2. Epub 2020 Nov 8.</citation>
      <PMID>33176180</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 9, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
      <investigator_full_name>Raul Nogueira</investigator_full_name>
      <investigator_title>Director, UPMC Stroke Institute</investigator_title>
    </responsible_party>
    <keyword>Stroke</keyword>
    <keyword>Ischemic</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>
    <patient_data>
      <sharing_ipd>No</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/NCT05983757
  org study id: STUDY23030032
  nct id: NCT05983757
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  A phase III, randomized, multi-center, investigational, open label clinical trial that will
        examine whether treatment with endovascular thrombectomy is superior to standard medical
        therapy alone in patients who suffer a Distal Medium Vessel Occlusion Ischemic Stroke within
        12 hours from time last seen well
  DUSK is a Phase-3, prospective, multicenter, investigational, randomized, controlled,
        open-label study with blinded endpoint evaluation (PROBE design) and an adaptive design with
        population enrichment. The randomization employs a 1:1 ratio of endovascular thrombectomy
        (EVT) versus standard medical management (SMM) in patients who suffer a distal medium vessel
        occlusion (DMVO) stroke within 12 hours from time last seen well (TLSW) and have evidence of
        salvageable brain tissue on perfusion imaging. Randomization will be done under a
        minimization process using age (≤67 vs. >67 years), baseline NIHSS (≤12 vs. >12), use of IV
        thrombolysis (none vs. within 120 minutes from randomization vs. > 120 minutes from
        randomization), site of occlusion (M2 vs. M3 vs. ACA vs. PCA), baseline infarct volume (≤15mL
        vs. >15-30mL vs. >30-50mL), perfusion mismatch volume (≤15mL vs. >15-30mL vs. >30-50mL),
        therapeutic window (0-4.5 vs. 4.5-8 or >9-12 hours after TLKW), and participating site. The
        candidate enriched populations that the trial considers are based on use of intravenous
        thrombolysis (none vs. within 120 minutes from randomization vs. > 120 minutes from
        randomization), TLKW to randomization (0-6 vs. 6-12 hours) and mismatch volumes as measured
        using absolute mismatch (defined as Tmax>6 sec - DWI lesion on MRI or Tmax>6 sec -rCBF<30%
        lesion on CTP) (>40 cc vs. >30cc vs. >20cc vs. >10cc). The primary endpoint will be a
        categorical shift across all levels on the modified Rankin Scale (mRS) at 90-days
        post-randomization. The hypothesis is that EVT will lead to an improved clinical outcome at
        90 days. Interim analysis will be performed after the primary endpoint is available for a
        total of 386 randomized patients.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: The randomization employs a 1:1 ratio of endovascular thrombectomy (EVT) with the use of Trevo NXT ProVue Retrievers, AXS Vecta 46 Intermediate Catheter and AXS Catalyst 5 Distal Access Catheter, versus standard medical management (SMM) in patients who suffer a distal medium vessel occlusion (DMVO) stroke within 12 hours from time last seen well (TLSW) and have evidence of salvageable brain tissue on perfusion imaging. Randomization will be done under a minimization process using age (≤67 vs. >67 years), baseline NIHSS (≤12 vs. >12), use of IV thrombolysis (none vs. within 120 minutes from randomization vs. > 120 minutes from randomization), site of occlusion (M2 vs. M3 vs. ACA vs. PCA), baseline infarct volume (≤15mL vs. >15-30mL vs. >30-50mL), perfusion mismatch volume (≤15mL vs. >15-30mL vs. >30-50mL), therapeutic window (0-4.5 vs. 4.5-8 or >9-12 hours after TLKW), and participating site.
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: One investigator or designee will remain blinded at each site to perform primary outcome assessment at Day 30 and Day 90.
  measure: Shift in distribution of all levels of the 90-day modified Rankin Scale with levels 5-6 combined (mRS; 0, 1, 2, 3, 4, 5-6) as assessed by structured assessment
  time frame: 90-day follow-up
  description: Modified Rankin Scale measurement (mRS): 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead
  measure: Shift in distribution of the 90-day mRS (0;1;2;3;4;5;6) as assessed by structured assessment
  time frame: 90-day follow-up
  description: Modified Rankin Scale measurement (mRS)0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead
  measure: Rates of Independent Outcome defined as mRS ≤2 and/ or equal to Baseline mRS at 90 days
  time frame: 90-day follow-up
  description: Independant outcome: 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead
  measure: Rates of Excellent Outcome defined as mRS ≤1 and/ or equal to Baseline mRS at 90 days
  time frame: 90-day follow-up
  description: Excellent outcome: 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead.
  measure: Rates of Good Functional Outcomes adjusted for the baseline mRS and stroke severity (NIHSS) according to the modified Rankin Scale scores at 90 days as following:
  time frame: 90-day follow-up
  description: NIHSS and mRS scores MRS: 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead NIHSS: 0=no stroke symptoms, 1-4=minor stroke, 5-15 moderate stroke, 16-20 moderate to sever stroke, 21-42- severe stroke.
  If NIHSS <10 and Baseline mRS 0 or 1: 90-day mRS ≤1
  If NIHSS <10 and Baseline mRS 2: 90-day mRS ≤2
  If NIHSS ≥10 and Baseline mRS 0 or 1: 90-day mRS ≤2
  If NIHSS ≥10 and Baseline mRS 2: 90-day mRS ≤3
  measure: EVT arm only: Final reperfusion grades according to the extended Thrombolysis in Cerebral Infarction (eTICI) scale and the rates of First Pass Effect (eTICI ≥2c) and Modified First Pass Effect (eTICI ≥2b50)
  time frame: 90-day follow-up
  description: Reprofusion grades :TICI scores:grade 0: no perfusion noted (0% reperfusion) grade 1: reduction in thrombus but without any resultant filling of distal arterial branches grade 2 grade 2a: reperfusion of 1-49% of the territory grade 2b50: reperfusion of 50-66% of the territory grade 2b67: reperfusion of 67-89% of the territory grade 2c: extensive reperfusion of 90-99% of the territory grade 3: complete or full reperfusion (100% reperfusion).
  measure: EVT arm only: Final reperfusion grades according to the rates of First Pass Effect (eTICI ≥2c)
  time frame: 90-Day follow up
  description: Reprofusion grades :TICI scores:grade 0: no perfusion noted (0% reperfusion) grade 1: reduction in thrombus but without any resultant filling of distal arterial branches grade 2 grade 2a: reperfusion of 1-49% of the territory grade 2b50: reperfusion of 50-66% of the territory grade 2b67: reperfusion of 67-89% of the territory grade 2c: extensive reperfusion of 90-99% of the territory grade 3: complete or full reperfusion (100% reperfusion).
  measure: EVT arm only: Final reperfusion grades according to the Modified First Pass Effect (eTICI ≥2b50)
  time frame: 90 day follow up
  description: Reprofusion grades :TICI scores:grade 0: no perfusion noted (0% reperfusion) grade 1: reduction in thrombus but without any resultant filling of distal arterial branches grade 2 grade 2a: reperfusion of 1-49% of the territory grade 2b50: reperfusion of 50-66% of the territory grade 2b67: reperfusion of 67-89% of the territory grade 2c: extensive reperfusion of 90-99% of the territory grade 3: complete or full reperfusion (100% reperfusion).
  measure: Mean score for disability on the utility-weighted modified Rankin scale (UW-mRS) at 90 days
  time frame: 90-day follow-up
  description: utility weighted mRS 0=no symptoms, 1= no significant disablity despite symptoms, able to carry out all usual duties. 2= slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance. 3=moderate disability, requiring some help, able to walk without assistance. 4=moderatly severe disability, unable to walk and attend to bodily needs without assistance. 5=severe disability, bedridden, incontinent and requiring total nursing care. 6=dead
  measure: Final infarct volume (FIV) (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 24 hours (-2/+12 hours)
  time frame: 24 hours (-2hours /+12 hours)
  description: Infarct volume at 24 hours will be measured on CT or MRI.
  measure: Final infarct growth (FIV - baseline infarct on CTP or DWI)
  time frame: 24 hours (-2 hours/+12 hours)
  description: Infarct volume at 24 hours will be measured on CT or MRI, growth of infarct from baseline to 24 hours will be captured.
  measure: Final infarct volume (FIV) and infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available)
  time frame: 3-5 days
  description: Infarct volume at 3-5 days will be measured on CT or MRI.
  measure: Final infarct growth (FIV - baseline infarct on CTP or DWI) evaluated on CT or MRI at 3-5 days (if available)
  time frame: 3 to 5 days
  description: Infarct volume at 3-5 days will be measured on CT or MRI, growth of infarct will be compared to baseline.
  measure: Clinical improvement at 24 hours calculated as the difference between 24-hour and baseline NIHSS score
  time frame: 24 hours
  description: NIHSS score at 24hours :NIHSS: 0=no stroke symptoms, 1-4=minor stroke, 5-15 moderate stroke, 16-20 moderate to sever stroke, 21-42- severe stroke.
  measure: Cost effectiveness analysis of endovascular thrombectomy vs standard medical therapy
  time frame: 90-day follow-up
  description: Assessment of costs from the time of randomization to the 90 day follow up. This includes Costs of hospitalization, institutional living and outpatient care will be assessed and compared for each arm.
  measure: Brain tissue reperfusion evaluated by CT or MRI perfusion at 24 hours in both treatment groups (if available)
  time frame: 24 hours
  description: CT or MRI results at 24 hours
  measure: Vessel patency evaluated by CTA or MRA perfusion at 24 hours in both treatment groups (if available)
  time frame: 24 hours
  description: CTA or MRA perfusion results at 24 hours
  measure: Patient reported outcomes (EQ-5D)
  time frame: 90-day follow-up
  description: Questionnaires assessed by blinded assessor at 90 days. EQ-5D measures mobility, self care, usual activities, pain and anxiety, overall heath is measured on a scale of 0 (worst health state) to 100 best health state.
  measure: Patient reported outcomes (PROMIS Global-10)
  time frame: 90 day follow up
  description: Questionnaires assessed by blinded assessor at 90 days. Promise Global Health measures current health status on a scale of 1=poor, 2=fair, 3=good, 4=very good, 5=excellent. The scale is from 1-5 with 1 being the poorest health outcome and 5 the best.
  measure: Patient reported outcomes (PROMIS Fatigue)
  time frame: 90 day follow up
  description: Questionnaires assessed by blinded assessor at 90 days. Promise Fatigue will measure degree of fatigue on a scale of 1=not at all, 2=a little bit, 3=somewhat, 4= quite a bit, 5=very much. The scale is from 1-5 with 1 being the least fatigued and 5 the greatest feeling of fatigue.
  measure: Patient reported outcomes ( IADL)
  time frame: 90 day follow up
  description: Questionnaires assessed by blinded assessor at 90 days. IADL measures the ability to use a telephone, shop prepare food, do housekeeping, laundry, mode of transportation, medications and handle finances. The subject will answer the questions and answer as for how they are able to accomplish their ADLs.
  measure: Patient reported outcomes ( MoCa)
  time frame: 90 day follow up
  description: Questionnaires assessed by blinded assessor at 90 days. MoCa measures the patient's ability to draw(visuospatial), name items, memory, attention, language, and abstraction. There are several questions that the subject will answer for each category.
  measure: All cause mortality
  time frame: 90 day follow up
  description: All-cause mortality within 90 days
  measure: Mortality due to stroke
  time frame: 90 day follow up
  description: Mortality within 90 days due to index stroke
  measure: Intracranial hemorrhage
  time frame: 90 day follow up
  description: Symptomatic intracranial hemorrhage (SICH) defined as per the modified SITS-MOST definition:local or remote parenchymal hemorrhage type 2, subarachnoid hemorrhage, and/or intraventricular hemorrhage on the post-treatment imaging scan, combined with a neurological deterioration of 4 points or more on the NIHSS from baseline, or from the lowest NIHSS value between baseline and 24 h (-2/+12), or leading to death that the CEC/DSMB judges is causative of the deterioration. (https://www.sitsinternational.org/research/studies/sits-most-ii/)
  measure: Intracranial hemorrhage
  time frame: 24 hours (-2 hours /+12 hours)
  description: The incidence of any intracranial hemorrhage measured at 24 (-2/+12) hours as graded by the central core-lab using the Heidelberg classification criteria.
  measure: Procedure-related vessel perforation.
  time frame: 24 hours (-2 hours /+12 hours)
  description: Perforation of the artery related to the procedure.
  measure: Procedure-related vessel dissection
  time frame: 24 hours (-2 hours/+12 hours)
  description: Dissection of an artery related to the procedure.
  measure: Embolization to a new territory during mechanical thrombectomy (MT) procedure
  time frame: 24 hours (-2 hours/+12hours)
  description: New emboli to a different area of the brain during the MR procedure.
  measure: Significant extracranial hemorrhage (e.g., access site, retroperitoneal hematoma) requiring blood transfusion and/or surgical intervention.
  time frame: 24 hours (-2 hours/+12 hours)
  description: Hemorrhage in other areas besides the brain such as the arterial access site or retroperitoneum.
  arm group label: Standard of Care Treatment
  arm group type: Active Comparator
  description: Standard medical management in patients who suffer a distal medium vessel occlusion
  arm group label: Endovascular Thrombectomy
  arm group type: Experimental
  description: Endovascular thrombectomy in patients who suffer a distal medium vessel occlusion.
  intervention type: Device
  intervention name: Experimental: endovascular thrombectomy in patients who suffer a distal medium vessel occlusion
  description: The AXS Catalyst Distal Access Catheter is indicated for use in facilitating the insertion and guidance of appropriately sized interventional devices into a selected blood vessel in the peripheral and neurovascular systems, and is also indicated for use as a conduit for retrieval devices.
  The AXS Vecta Intermediate Catheter, as part of the AXS Vecta Aspiration System, is indicated in the revascularization of patients with acute ischemic stroke. Patients who are ineligible for intravenous tissue plasminogen activator (IV t-PA) or who failed IV t-PA therapy are candidates for treatment.
  The Trevo® Retriever is indicated for use to restore blood flow in the neurovasculature by removing thrombus for the treatment of acute ischemic stroke to reduce disability in patients with a persistent, proximal anterior circulation, large vessel occlusion, and smaller core infarcts who have first received intravenous tissue plasminogen activator (IV t-PA).
  arm group label: Endovascular Thrombectomy
  other name: AXS Vecta 46
  other name: AXS CAT 5
  other name: NXT ProVue Retriever
  intervention type: Other
  intervention name: Standard medical management
  description: All subjects should receive the best standard medical therapy based on current AHA guidelines. Subjects randomized to standard medical management (SMM) will receive standard medical therapy only based on the guidelines. All subjects are expected to be admitted to hospital as part of routine best guideline-based care and treated on a stroke unit or neurointensive care unit or equivalent.
  arm group label: Standard of Care Treatment
  other name: Active Comparator
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Raul G Nogueira, MD
  role: Principal Investigator
  affiliation: University of Pittsburgh
  last name: Denise McCarthy, MPPM RN
  phone: 1-878-261-6015
  email: mccarthydj@upmc.edu
  last name: Emma Gyurisin, MPH
  phone: 4126779128
  email: gyurisinek2@upmc.edu
  facility: 
  contact: 
  investigator: 
  country: United States
  citation: Ospel JM, Goyal M. A review of endovascular treatment for medium vessel occlusion stroke. J Neurointerv Surg. 2021 Jul;13(7):623-630. doi: 10.1136/neurintsurg-2021-017321. Epub 2021 Feb 26.
  PMID: 33637570
  citation: Saver JL, Chapot R, Agid R, Hassan A, Jadhav AP, Liebeskind DS, Lobotesis K, Meila D, Meyer L, Raphaeli G, Gupta R; Distal Thrombectomy Summit Group*dagger. Thrombectomy for Distal, Medium Vessel Occlusions: A Consensus Statement on Present Knowledge and Promising Directions. Stroke. 2020 Sep;51(9):2872-2884. doi: 10.1161/STROKEAHA.120.028956. Epub 2020 Aug 6. No abstract available. Erratum In: Stroke. 2020 Oct;51(10):e296.
  PMID: 32757757
  citation: Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30. Erratum In: Stroke. 2019 Dec;50(12):e440-e441.
  PMID: 31662037
  citation: Turc G, Bhogal P, Fischer U, Khatri P, Lobotesis K, Mazighi M, Schellinger PD, Toni D, de Vries J, White P, Fiehler J. European Stroke Organisation (ESO) - European Society for Minimally Invasive Neurological Therapy (ESMINT) Guidelines on Mechanical Thrombectomy in Acute Ischaemic StrokeEndorsed by Stroke Alliance for Europe (SAFE). Eur Stroke J. 2019 Mar;4(1):6-12. doi: 10.1177/2396987319832140. Epub 2019 Feb 26.
  PMID: 31165090
  citation: Campbell BCV, Ma H, Ringleb PA, Parsons MW, Churilov L, Bendszus M, Levi CR, Hsu C, Kleinig TJ, Fatar M, Leys D, Molina C, Wijeratne T, Curtze S, Dewey HM, Barber PA, Butcher KS, De Silva DA, Bladin CF, Yassi N, Pfaff JAR, Sharma G, Bivard A, Desmond PM, Schwab S, Schellinger PD, Yan B, Mitchell PJ, Serena J, Toni D, Thijs V, Hacke W, Davis SM, Donnan GA; EXTEND, ECASS-4, and EPITHET Investigators. Extending thrombolysis to 4.5-9 h and wake-up stroke using perfusion imaging: a systematic review and meta-analysis of individual patient data. Lancet. 2019 Jul 13;394(10193):139-147. doi: 10.1016/S0140-6736(19)31053-0. Epub 2019 May 22. Erratum In: Lancet. 2020 Jun 20;395(10241):1906.
  PMID: 31128925
  citation: Ospel JM, Menon BK, Demchuk AM, Almekhlafi MA, Kashani N, Mayank A, Fainardi E, Rubiera M, Khaw A, Shankar JJ, Dowlatshahi D, Puig J, Sohn SI, Ahn SH, Poppe A, Calleja A, Hill MD, Goyal M. Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment. Stroke. 2020 Nov;51(11):3232-3240. doi: 10.1161/STROKEAHA.120.030227. Epub 2020 Oct 19.
  PMID: 33070714
  citation: Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.
  PMID: 26898852
  citation: Menon BK, Hill MD, Davalos A, Roos YBWEM, Campbell BCV, Dippel DWJ, Guillemin F, Saver JL, van der Lugt A, Demchuk AM, Muir K, Brown S, Jovin T, Mitchell P, White P, Bracard S, Goyal M. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration. J Neurointerv Surg. 2019 Nov;11(11):1065-1069. doi: 10.1136/neurintsurg-2018-014678. Epub 2019 Apr 11.
  PMID: 30975736
  citation: Haussen DC, Lima A, Nogueira RG. The Trevo XP 3x20 mm retriever ('Baby Trevo') for the treatment of distal intracranial occlusions. J Neurointerv Surg. 2016 Mar;8(3):295-9. doi: 10.1136/neurintsurg-2014-011613. Epub 2015 May 6.
  PMID: 25948592
  citation: Haussen DC, Al-Bayati AR, Eby B, Ravindran K, Rodrigues GM, Frankel MR, Nogueira RG. Blind exchange with mini-pinning technique for distal occlusion thrombectomy. J Neurointerv Surg. 2020 Apr;12(4):392-395. doi: 10.1136/neurintsurg-2019-015205. Epub 2019 Aug 31.
  PMID: 31473647
  citation: Perez-Garcia C, Moreu M, Rosati S, Simal P, Egido JA, Gomez-Escalonilla C, Arrazola J. Mechanical Thrombectomy in Medium Vessel Occlusions: Blind Exchange With Mini-Pinning Technique Versus Mini Stent Retriever Alone. Stroke. 2020 Nov;51(11):3224-3231. doi: 10.1161/STROKEAHA.120.030815. Epub 2020 Oct 19.
  PMID: 33070712
  citation: Grossberg JA, Rebello LC, Haussen DC, Bouslama M, Bowen M, Barreira CM, Belagaje SR, Frankel MR, Nogueira RG. Beyond Large Vessel Occlusion Strokes: Distal Occlusion Thrombectomy. Stroke. 2018 Jul;49(7):1662-1668. doi: 10.1161/STROKEAHA.118.020567. Epub 2018 Jun 18. Erratum In: Stroke. 2018 Sep;49(9):e298.
  PMID: 29915125
  citation: Nogueira RG, Mohammaden MH, Haussen DC, Budzik RF, Gupta R, Krajina A, English JD, Malek AR, Sarraj A, Narata AP, Taqi MA, Frankel MR, Miller TR, Grobelny T, Baxter BW, Bartolini BM, Jenkins P, Estrade L, Liebeskind D, Veznedaroglu E; Trevo Registry Investigators. Endovascular therapy in the distal neurovascular territory: results of a large prospective registry. J Neurointerv Surg. 2021 Nov;13(11):979-984. doi: 10.1136/neurintsurg-2020-016851. Epub 2020 Dec 15.
  PMID: 33323503
  citation: Goyal M, Ospel JM, Menon BK, Hill MD. MeVO: the next frontier? J Neurointerv Surg. 2020 Jun;12(6):545-547. doi: 10.1136/neurintsurg-2020-015807. Epub 2020 Feb 14. No abstract available.
  PMID: 32060151
  citation: Seners P, Turc G, Maier B, Mas JL, Oppenheim C, Baron JC. Incidence and Predictors of Early Recanalization After Intravenous Thrombolysis: A Systematic Review and Meta-Analysis. Stroke. 2016 Sep;47(9):2409-12. doi: 10.1161/STROKEAHA.116.014181. Epub 2016 Jul 26.
  PMID: 27462117
  citation: Menon BK, Al-Ajlan FS, Najm M, Puig J, Castellanos M, Dowlatshahi D, Calleja A, Sohn SI, Ahn SH, Poppe A, Mikulik R, Asdaghi N, Field TS, Jin A, Asil T, Boulanger JM, Smith EE, Coutts SB, Barber PA, Bal S, Subramanian S, Mishra S, Trivedi A, Dey S, Eesa M, Sajobi T, Goyal M, Hill MD, Demchuk AM; INTERRSeCT Study Investigators. Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke. JAMA. 2018 Sep 11;320(10):1017-1026. doi: 10.1001/jama.2018.12498.
  PMID: 30208455
  citation: Tian H, Parsons MW, Levi CR, Lin L, Aviv RI, Spratt NJ, Butcher KS, Lou M, Kleinig TJ, Bivard A. Influence of occlusion site and baseline ischemic core on outcome in patients with ischemic stroke. Neurology. 2019 Jun 4;92(23):e2626-e2643. doi: 10.1212/WNL.0000000000007553. Epub 2019 May 1.
  PMID: 31043475
  citation: Lima FO, Furie KL, Silva GS, Lev MH, Camargo EC, Singhal AB, Harris GJ, Halpern EF, Koroshetz WJ, Smith WS, Nogueira RG. Prognosis of untreated strokes due to anterior circulation proximal intracranial arterial occlusions detected by use of computed tomography angiography. JAMA Neurol. 2014 Feb;71(2):151-7. doi: 10.1001/jamaneurol.2013.5007.
  PMID: 24323077
  citation: Thomalla G, Simonsen CZ, Boutitie F, Andersen G, Berthezene Y, Cheng B, Cheripelli B, Cho TH, Fazekas F, Fiehler J, Ford I, Galinovic I, Gellissen S, Golsari A, Gregori J, Gunther M, Guibernau J, Hausler KG, Hennerici M, Kemmling A, Marstrand J, Modrau B, Neeb L, Perez de la Ossa N, Puig J, Ringleb P, Roy P, Scheel E, Schonewille W, Serena J, Sunaert S, Villringer K, Wouters A, Thijs V, Ebinger M, Endres M, Fiebach JB, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Gerloff C; WAKE-UP Investigators. MRI-Guided Thrombolysis for Stroke with Unknown Time of Onset. N Engl J Med. 2018 Aug 16;379(7):611-622. doi: 10.1056/NEJMoa1804355. Epub 2018 May 16.
  PMID: 29766770
  citation: Ma H, Campbell BCV, Parsons MW, Churilov L, Levi CR, Hsu C, Kleinig TJ, Wijeratne T, Curtze S, Dewey HM, Miteff F, Tsai CH, Lee JT, Phan TG, Mahant N, Sun MC, Krause M, Sturm J, Grimley R, Chen CH, Hu CJ, Wong AA, Field D, Sun Y, Barber PA, Sabet A, Jannes J, Jeng JS, Clissold B, Markus R, Lin CH, Lien LM, Bladin CF, Christensen S, Yassi N, Sharma G, Bivard A, Desmond PM, Yan B, Mitchell PJ, Thijs V, Carey L, Meretoja A, Davis SM, Donnan GA; EXTEND Investigators. Thrombolysis Guided by Perfusion Imaging up to 9 Hours after Onset of Stroke. N Engl J Med. 2019 May 9;380(19):1795-1803. doi: 10.1056/NEJMoa1813046. Erratum In: N Engl J Med. 2021 Apr 1;384(13):1278.
  PMID: 31067369
  citation: Thomalla G, Boutitie F, Ma H, Koga M, Ringleb P, Schwamm LH, Wu O, Bendszus M, Bladin CF, Campbell BCV, Cheng B, Churilov L, Ebinger M, Endres M, Fiebach JB, Fukuda-Doi M, Inoue M, Kleinig TJ, Latour LL, Lemmens R, Levi CR, Leys D, Miwa K, Molina CA, Muir KW, Nighoghossian N, Parsons MW, Pedraza S, Schellinger PD, Schwab S, Simonsen CZ, Song SS, Thijs V, Toni D, Hsu CY, Wahlgren N, Yamamoto H, Yassi N, Yoshimura S, Warach S, Hacke W, Toyoda K, Donnan GA, Davis SM, Gerloff C; Evaluation of unknown Onset Stroke thrombolysis trials (EOS) investigators. Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data. Lancet. 2020 Nov 14;396(10262):1574-1584. doi: 10.1016/S0140-6736(20)32163-2. Epub 2020 Nov 8.
  PMID: 33176180
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Pittsburgh
  investigator full name: Raul Nogueira
  investigator title: Director, UPMC Stroke Institute
  mesh term: Stroke
  mesh term: Ischemic Stroke
  mesh term: Ischemia
  sharing ipd: No