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/NCT06034847</url>
    </required_header>
    <id_info>
      <org_study_id>2024-11741</org_study_id>
      <nct_id>NCT06034847</nct_id>
    </id_info>
    <brief_title>Treatment of Persistent Distal Occlusion After Successful Proximal Recanalization in Thrombectomy</brief_title>
    <acronym>2BE3</acronym>
    <official_title>Treatment of Persistent Distal Occlusion After Successful Proximal Recanalization in Thrombectomy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Centre hospitalier de l'Université de Montréal (CHUM)</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Centre hospitalier de l'Université de Montréal (CHUM)</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        In stroke patients, mechanical thrombectomy is now the standard of care when the stroke is&#xD;
        due to large proximal cerebral vessel occlusion. The purpose of the 2BE3 trial is to test&#xD;
        whether adjunct rescue treatment of persisting distal occlusions after successful proximal&#xD;
        recanalization of the large vessel occlusion can be proposed as an additional intervention to&#xD;
        restore reperfusion of affected stroke tissue and improve clinical outcomes.&#xD;
  &#xD;
        The rescue therapies will be either mechanical (small stent retrievers and/or small&#xD;
        aspiration catheters) or pharmacological (infusion of intra-arterial thrombolytics).&#xD;
  &#xD;
        Patients will be randomized to conservative management (mechanical thrombectomy with or&#xD;
        without IV thrombolytics of large proximal vessels) or rescue therapy (mechanical or&#xD;
        pharmacological interventions in distal vessels in addition to conservative management). Each&#xD;
        patient will be followed for 3 months post-intervention.&#xD;
  &#xD;
        The data collected will be clinical assessments and angiographic imaging to evaluate the&#xD;
        reperfusion state.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The purpose of the 2BE3 trial is to provide a clinical trial context for the use of rescue&#xD;
        therapy (mechanical or pharmacological therapies) in patients with persistent distal&#xD;
        occlusions after treatment of large vessel occlusions with mechanical thrombectomy and IV&#xD;
        thrombolytics. The main hypothesis is that rescue therapy with mechanical or pharmacological&#xD;
        therapies, compared with conservative management would result in improved clinical and&#xD;
        reperfusion scores at 90 days.&#xD;
  &#xD;
        The extent of reperfusion is an interesting therapeutic target because reperfusion status is&#xD;
        a strong indicator of clinical outcome: grades of better reperfusion are incrementally&#xD;
        associated with better clinical outcomes. Despite increased expertise of neuro-interventional&#xD;
        teams and the evolution in thrombectomy devices, incomplete reperfusion occurs in almost half&#xD;
        of patients undergoing treatment of large vessel occlusions. Thus, complementary treatments&#xD;
        targeting distal occlusions and known as &quot;rescue therapy&quot; have been introduced to reach&#xD;
        complete or near complete reperfusion.&#xD;
  &#xD;
        The devices and techniques proposed as rescue therapies include small stent retrievers, small&#xD;
        aspiration catheters and intra-arterial thrombolytics. Case studies and registries have shown&#xD;
        high reperfusion rates and low rates of periprocedural complications; however, there is lack&#xD;
        of randomized data to show the impact of rescue therapies on patient outcomes and safety&#xD;
        compared to conservative management (treatment of large vessel occlusions only). A randomized&#xD;
        clinical trial is therefore needed.&#xD;
  &#xD;
        The 2BE3 trial is a simple randomized trial designed to be integrated into daily clinical&#xD;
        practice. It will address whether rescue therapies truly offer a safe and more effective&#xD;
        alternative to conservative management. Selection criteria are loose in order to be of use to&#xD;
        most patients. Endpoints are simple, clinical, meaningful, valuable and resistant to bias. It&#xD;
        includes no extra risk or cost of visits beyond what is required in routine care.&#xD;
  &#xD;
        The design is multicenter, prospective, randomized, controlled, open-label study with blinded&#xD;
        evaluation (PROBE design). The study population is acute ischemic stroke patients with&#xD;
        persistent distal occlusions after treatment of large vessel occlusion with mechanical&#xD;
        thrombectomy and/or intravenous thrombolysis. The total number of patients will be 300, 150&#xD;
        in each arm, each followed for 3 months post-intervention.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 2024</start_date>
    <completion_date type="Anticipated">January 2029</completion_date>
    <primary_completion_date type="Anticipated">January 2028</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>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Rate of modified Rankin Scale score of 0-2. The modified Rankin score goes from 0 (no symptoms) to 6 (death). Higher scores mean a worse outcome</measure>
      <time_frame>90 days</time_frame>
      <description>proportion of patients with a modified Rankin Scale score of 0-2</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>score on the modified Rankin Scale. The modified Rankin score goes from 0 (no symptoms) to 6 (death). Higher scores mean a worse outcome</measure>
      <time_frame>90 days</time_frame>
      <description>score on the modified Rankin Scale</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of functional independence</measure>
      <time_frame>90 days</time_frame>
      <description>Functional independence is defined as a modified Rankin Scale score of 0-2</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in NIHSS (National Institutes of Health Stroke Score) score. The scale goes from 0 to 42; higher scores indicated worse outcomes.</measure>
      <time_frame>24 hours</time_frame>
      <description>Difference between the NIHSS score at Registration and at 24 hours post-intervention</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of NIHSS (National Institutes of Health Stroke Score) score improvement. The scale goes from 0 to 42; higher scores indicated worse outcomes.</measure>
      <time_frame>24 hours</time_frame>
      <description>Rate of decrease of 4 points or more in NIHSS score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of improved global ipsilateral hemispheric reperfusion</measure>
      <time_frame>at end of procedure</time_frame>
      <description>blinded assessment of reperfusion on angiogram as measured by the modified TICI (Thrombolysis in Cerebral Infarction) scale. The scale goes from 0 to 3; higher scores indicate better outcomes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of reperfusion</measure>
      <time_frame>at end of procedure</time_frame>
      <description>assessed by the modified TICI (Thrombolysis in Cerebral Infarction) scale on angiogram. The scale goes from 0 to 3; higher scores indicate better outcomes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of complete reperfusion</measure>
      <time_frame>at end of procedure</time_frame>
      <description>a modified TICI (Thrombolysis in Cerebral Infarction) score of 3 on angiogram. The scale goes from 0 to 3; higher scores indicate better outcomes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Procedure time</measure>
      <time_frame>at end of procedure</time_frame>
      <description>elapsed time from arterial puncture to last angiogram</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of thrombectomy passes</measure>
      <time_frame>at end of procedure</time_frame>
      <description>Number of thrombectomy passes to achieve final reperfusion</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Mortality rate</measure>
      <time_frame>24 hours and 90 days</time_frame>
      <description>Rate of mortality</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of procedural complications</measure>
      <time_frame>at end of procedure</time_frame>
      <description>defined as: vascular perforation, arterial dissection, new territory emboli, access site complication requiring surgical repair, subarachnoid hemorrhage</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of symptomatic intracerebral hemorrhage</measure>
      <time_frame>24 hours</time_frame>
      <description>hemorrhage on CT or MRI according to the Heidelberg classification associated with a 4 point or greater worsening on the NIHSS score. The Heidelberg classification goes from 1 to 3d; higher scores indicate worse outcomes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Rate of any intracranial hemorrhage</measure>
      <time_frame>24 hours</time_frame>
      <description>hemorrhage on CT or MRI according to the Heidelberg classification. The Heidelberg classification goes from 1 to 3d; higher scores indicate worse outcomes.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">300</enrollment>
    <condition>Stroke, Acute Thrombotic</condition>
    <arm_group>
      <arm_group_label>Conservative management</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Mechanical thrombectomy of large vessel occlusions with or without administration of IV thrombolytics</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Rescue therapy</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>In addition to conservative management, rescue therapy in distal occlusions consisting of either mechanical thrombectomy with small stent retrievers with or without contact aspiration, or intra-arterial pharmacotherapy with tPA (tissue Plasminogen Activator), uPA (urokinase Plasminogen Activator) or tenecteplase.</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Mechanical thrombectomy in proximal large vessels</intervention_name>
      <description>mechanical thrombectomy with retrievable stents to remove clots in proximal large vessels, combined or not with distal aspiration, combined or not with IV thrombolytics</description>
      <arm_group_label>Conservative management</arm_group_label>
      <arm_group_label>Rescue therapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Rescue mechanical thrombectomy in distal vessels</intervention_name>
      <description>In addition to mechanical thrombectomy in proximal large vessels, mechanical thrombectomy in distal vessels with small stent retrievers combined or not with contact aspiration, or intra-arterial perfusion of thrombolytics such as tPA or uPA or tenecpeplase</description>
      <arm_group_label>Rescue therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  any patient with a large vessel occlusion in the M1 or M2 segment of the MCA (Middle&#xD;
               Cerebral Artery), supraclinoid ICA (Internal Carotid Artery), or basilar artery who is&#xD;
               a candidate for thrombectomy&#xD;
  &#xD;
            -  with a persistent distal occlusion in M2-M4, A1-A5, P1-P5 after successful&#xD;
               recanalization of the proximal clot with mechanical thrombectomy and/or IV&#xD;
               thrombolysis&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  poor 3 month prognosis from comorbidities&#xD;
  &#xD;
            -  evidence of active bleeding on examination&#xD;
  &#xD;
            -  recent surgery with a significant risk of bleeding&#xD;
  &#xD;
            -  VKA (Vitamin K Antagonists) oral anticoagulation with INR (International Normalized&#xD;
               Ratio) - &gt; 1.7&#xD;
  &#xD;
            -  curative heparin or direct oral anticoagulants in previous 48 hours&#xD;
  &#xD;
            -  platelet count &lt; 100 000/mm3&#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>Daniela Iancu, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Centre hospitalier de l'Université de Montréal (CHUM)</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Daniela Iancu, MD</last_name>
      <phone>15148908000</phone>
      <phone_ext>8450</phone_ext>
      <email>daniela.iancu.med@ssss.gouv.qc.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Guylaine Gevry, BSc</last_name>
      <phone>15148908000</phone>
      <phone_ext>27235</phone_ext>
      <email>guylaine.gevry.chum@ssss.gouv.qc.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>CHUM - Centre Hospitalier de l'Université de Montréal</name>
        <address>
          <city>Montréal</city>
          <state>Quebec</state>
          <zip>H2X 0A9</zip>
          <country>Canada</country>
        </address>
      </facility>
      <contact>
        <last_name>Guylaine Gevry, BSc</last_name>
        <phone>15148908000</phone>
        <phone_ext>27235</phone_ext>
        <email>guylaine.gevry.chum@ssss.gouv.qc.ca</email>
      </contact>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 5, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Large vessel occlusion</keyword>
    <keyword>Persistent distal occlusion</keyword>
    <keyword>Mechanical thrombectomy</keyword>
    <keyword>Intra-arterial thrombolytics</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Stroke</mesh_term>
      <mesh_term>Thrombotic Stroke</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
      <ipd_description>there is no plan to share individual participant data</ipd_description>
    </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/NCT06034847
  org study id: 2024-11741
  nct id: NCT06034847
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  In stroke patients, mechanical thrombectomy is now the standard of care when the stroke is
        due to large proximal cerebral vessel occlusion. The purpose of the 2BE3 trial is to test
        whether adjunct rescue treatment of persisting distal occlusions after successful proximal
        recanalization of the large vessel occlusion can be proposed as an additional intervention to
        restore reperfusion of affected stroke tissue and improve clinical outcomes.
  
        The rescue therapies will be either mechanical (small stent retrievers and/or small
        aspiration catheters) or pharmacological (infusion of intra-arterial thrombolytics).
  
        Patients will be randomized to conservative management (mechanical thrombectomy with or
        without IV thrombolytics of large proximal vessels) or rescue therapy (mechanical or
        pharmacological interventions in distal vessels in addition to conservative management). Each
        patient will be followed for 3 months post-intervention.
  
        The data collected will be clinical assessments and angiographic imaging to evaluate the
        reperfusion state.
  The purpose of the 2BE3 trial is to provide a clinical trial context for the use of rescue
        therapy (mechanical or pharmacological therapies) in patients with persistent distal
        occlusions after treatment of large vessel occlusions with mechanical thrombectomy and IV
        thrombolytics. The main hypothesis is that rescue therapy with mechanical or pharmacological
        therapies, compared with conservative management would result in improved clinical and
        reperfusion scores at 90 days.
  
        The extent of reperfusion is an interesting therapeutic target because reperfusion status is
        a strong indicator of clinical outcome: grades of better reperfusion are incrementally
        associated with better clinical outcomes. Despite increased expertise of neuro-interventional
        teams and the evolution in thrombectomy devices, incomplete reperfusion occurs in almost half
        of patients undergoing treatment of large vessel occlusions. Thus, complementary treatments
        targeting distal occlusions and known as "rescue therapy" have been introduced to reach
        complete or near complete reperfusion.
  
        The devices and techniques proposed as rescue therapies include small stent retrievers, small
        aspiration catheters and intra-arterial thrombolytics. Case studies and registries have shown
        high reperfusion rates and low rates of periprocedural complications; however, there is lack
        of randomized data to show the impact of rescue therapies on patient outcomes and safety
        compared to conservative management (treatment of large vessel occlusions only). A randomized
        clinical trial is therefore needed.
  
        The 2BE3 trial is a simple randomized trial designed to be integrated into daily clinical
        practice. It will address whether rescue therapies truly offer a safe and more effective
        alternative to conservative management. Selection criteria are loose in order to be of use to
        most patients. Endpoints are simple, clinical, meaningful, valuable and resistant to bias. It
        includes no extra risk or cost of visits beyond what is required in routine care.
  
        The design is multicenter, prospective, randomized, controlled, open-label study with blinded
        evaluation (PROBE design). The study population is acute ischemic stroke patients with
        persistent distal occlusions after treatment of large vessel occlusion with mechanical
        thrombectomy and/or intravenous thrombolysis. The total number of patients will be 300, 150
        in each arm, each followed for 3 months post-intervention.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: Rate of modified Rankin Scale score of 0-2. The modified Rankin score goes from 0 (no symptoms) to 6 (death). Higher scores mean a worse outcome
  time frame: 90 days
  description: proportion of patients with a modified Rankin Scale score of 0-2
  measure: score on the modified Rankin Scale. The modified Rankin score goes from 0 (no symptoms) to 6 (death). Higher scores mean a worse outcome
  time frame: 90 days
  description: score on the modified Rankin Scale
  measure: Rate of functional independence
  time frame: 90 days
  description: Functional independence is defined as a modified Rankin Scale score of 0-2
  measure: Change in NIHSS (National Institutes of Health Stroke Score) score. The scale goes from 0 to 42; higher scores indicated worse outcomes.
  time frame: 24 hours
  description: Difference between the NIHSS score at Registration and at 24 hours post-intervention
  measure: Rate of NIHSS (National Institutes of Health Stroke Score) score improvement. The scale goes from 0 to 42; higher scores indicated worse outcomes.
  time frame: 24 hours
  description: Rate of decrease of 4 points or more in NIHSS score
  measure: Rate of improved global ipsilateral hemispheric reperfusion
  time frame: at end of procedure
  description: blinded assessment of reperfusion on angiogram as measured by the modified TICI (Thrombolysis in Cerebral Infarction) scale. The scale goes from 0 to 3; higher scores indicate better outcomes
  measure: Rate of reperfusion
  time frame: at end of procedure
  description: assessed by the modified TICI (Thrombolysis in Cerebral Infarction) scale on angiogram. The scale goes from 0 to 3; higher scores indicate better outcomes
  measure: Rate of complete reperfusion
  time frame: at end of procedure
  description: a modified TICI (Thrombolysis in Cerebral Infarction) score of 3 on angiogram. The scale goes from 0 to 3; higher scores indicate better outcomes
  measure: Procedure time
  time frame: at end of procedure
  description: elapsed time from arterial puncture to last angiogram
  measure: Number of thrombectomy passes
  time frame: at end of procedure
  description: Number of thrombectomy passes to achieve final reperfusion
  measure: Mortality rate
  time frame: 24 hours and 90 days
  description: Rate of mortality
  measure: Rate of procedural complications
  time frame: at end of procedure
  description: defined as: vascular perforation, arterial dissection, new territory emboli, access site complication requiring surgical repair, subarachnoid hemorrhage
  measure: Rate of symptomatic intracerebral hemorrhage
  time frame: 24 hours
  description: hemorrhage on CT or MRI according to the Heidelberg classification associated with a 4 point or greater worsening on the NIHSS score. The Heidelberg classification goes from 1 to 3d; higher scores indicate worse outcomes.
  measure: Rate of any intracranial hemorrhage
  time frame: 24 hours
  description: hemorrhage on CT or MRI according to the Heidelberg classification. The Heidelberg classification goes from 1 to 3d; higher scores indicate worse outcomes.
  arm group label: Conservative management
  arm group type: Active Comparator
  description: Mechanical thrombectomy of large vessel occlusions with or without administration of IV thrombolytics
  arm group label: Rescue therapy
  arm group type: Active Comparator
  description: In addition to conservative management, rescue therapy in distal occlusions consisting of either mechanical thrombectomy with small stent retrievers with or without contact aspiration, or intra-arterial pharmacotherapy with tPA (tissue Plasminogen Activator), uPA (urokinase Plasminogen Activator) or tenecteplase.
  intervention type: Device
  intervention name: Mechanical thrombectomy in proximal large vessels
  description: mechanical thrombectomy with retrievable stents to remove clots in proximal large vessels, combined or not with distal aspiration, combined or not with IV thrombolytics
  arm group label: Conservative management
  arm group label: Rescue therapy
  intervention type: Device
  intervention name: Rescue mechanical thrombectomy in distal vessels
  description: In addition to mechanical thrombectomy in proximal large vessels, mechanical thrombectomy in distal vessels with small stent retrievers combined or not with contact aspiration, or intra-arterial perfusion of thrombolytics such as tPA or uPA or tenecpeplase
  arm group label: Rescue therapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Daniela Iancu, MD
  role: Principal Investigator
  affiliation: Centre hospitalier de l'Université de Montréal (CHUM)
  last name: Daniela Iancu, MD
  phone: 15148908000
  phone ext: 8450
  email: daniela.iancu.med@ssss.gouv.qc.ca
  last name: Guylaine Gevry, BSc
  phone: 15148908000
  phone ext: 27235
  email: guylaine.gevry.chum@ssss.gouv.qc.ca
  facility: 
  contact: 
  country: Canada
  responsible party type: Sponsor
  mesh term: Stroke
  mesh term: Thrombotic Stroke
  sharing ipd: No
  ipd description: there is no plan to share individual participant data