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/NCT05963698</url>
    </required_header>
    <id_info>
      <org_study_id>LAAOS-4</org_study_id>
      <nct_id>NCT05963698</nct_id>
    </id_info>
    <brief_title>The Fourth Left Atrial Appendage Occlusion Study</brief_title>
    <acronym>LAAOS-4</acronym>
    <official_title>The Fourth Left Atrial Appendage Occlusion Study (LAAOS-4)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hamilton Health Sciences Corporation</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>McMaster University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Population Health Research Institute</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Boston Scientific Corporation</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Hamilton Health Sciences Corporation</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>
        LAAOS-4 aims to determine if catheter-based endovascular left atrial appendage occlusion&#xD;
        prevents ischemic stroke or systemic embolism in participants with atrial fibrillation, who&#xD;
        remain at high risk of stroke, despite receiving ongoing treatment with oral anticoagulation.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        LAAOS-4 is a multicentre, prospective, open-label, randomized controlled trial with blinded&#xD;
        assessment of endpoints (PROBE) to determine if catheter-based endovascular left atrial&#xD;
        appendage occlusion prevents ischemic stroke or systemic embolism in participants with atrial&#xD;
        fibrillation, who remain at high risk of stroke, despite receiving ongoing treatment with&#xD;
        oral anticoagulation.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 1, 2029</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2029</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>Randomized Controlled Trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
      <masking_description>Events Adjudication Committee is blinded to intervention assignment.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Ischemic stroke or systemic embolism</measure>
      <time_frame>The study duration is event-driven. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>The primary efficacy variable is the time from randomization to first occurrence of any of the components of the composite outcome (adjudicated) over the duration of follow-up, including:&#xD;
  Ischemic stroke (Strokes of undetermined etiology will be treated as ischemic stroke)&#xD;
  Systemic embolism</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>All-cause stroke or systemic embolism</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Secondary efficacy outcomes will be evaluated in a hierarchical fashion only when the primary outcome meets statistical significance in the specified order:&#xD;
  Time from randomization to first occurrence of all-cause stroke or systemic embolism</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All-cause stroke, systemic embolism, or transient ischemic attack (TIA)</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Time from randomization to first occurrence of all-cause stroke, systemic embolism or transient ischemic attack (TIA)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Montreal Cognitive Assessment (MoCA) Score</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Proportion of participants with a decrease of two or more points on the MoCA score at either year 2 or end of study</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>New disabling ischemic strokes</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Time from randomization to first occurrence of disabling ischemic strokes with modified Rankin Score (mRS) &gt;2, measured at 90 days post-stroke</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular mortality</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Time from randomization to cardiovascular mortality</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All-cause mortality</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Time from randomization to all-cause mortality</description>
    </secondary_outcome>
    <other_outcome>
      <measure>Non-procedural Major Bleeding</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Proportion of participants with non-procedural Major Bleeding (International Society on Thrombosis and Haemostasis (ISTH) definition; excluding WATCHMAN-related bleeding within 14 days of implant)</description>
    </other_outcome>
    <other_outcome>
      <measure>Hospitalization for any cause</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Time from randomization to first occurrence of hospitalization for any cause</description>
    </other_outcome>
    <other_outcome>
      <measure>Heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Time from randomization to first occurrence of heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy</description>
    </other_outcome>
    <other_outcome>
      <measure>Myocardial Infarction</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Time from randomization to first occurrence of Myocardial Infarction (4th Universal definition)</description>
    </other_outcome>
    <other_outcome>
      <measure>Device and procedural-related outcomes: Device-related thrombus</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Proportion of participants with device-related thrombus (thrombus formed on the surface of the WATCHMAN device)</description>
    </other_outcome>
    <other_outcome>
      <measure>Device and procedural-related outcomes: Incomplete left atrial appendage (LAA) closure</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Proportion of participants with incomplete LAA closure</description>
    </other_outcome>
    <other_outcome>
      <measure>Device and procedural-related outcomes: Peri-procedural major bleeding</measure>
      <time_frame>Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).</time_frame>
      <description>Proportion of participants with peri-procedural major bleeding (ISTH definition; within 14 days following the procedure)</description>
    </other_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">4000</enrollment>
    <condition>Atrial Fibrillation</condition>
    <condition>Stroke, Ischemic</condition>
    <condition>Systemic Embolism</condition>
    <arm_group>
      <arm_group_label>WATCHMAN device</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard Care</arm_group_label>
      <arm_group_type>No Intervention</arm_group_type>
      <description>Participants will receive local, standard medical care</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>WATCHMAN device</intervention_name>
      <description>Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device</description>
      <arm_group_label>WATCHMAN device</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. (a) Persistent or permanent atrial fibrillation OR (b) Paroxysmal atrial fibrillation&#xD;
               in participants with a history of ischemic stroke or systemic embolism&#xD;
  &#xD;
            2. Increased risk of stroke, defined as a CHA2DS2-VASc stroke risk score of ≥ 4. [Note:&#xD;
               the acronym CHA2DS2-VASc stands for congestive heart failure, hypertension, age ≥75&#xD;
               (doubled), diabetes, stroke (doubled), vascular disease, age 65 to 74 and sex category&#xD;
               (female).]&#xD;
  &#xD;
            3. Treatment with oral anticoagulants (Vitamin K agonist or factor Xa inhibitor) for at&#xD;
               least 90 days prior to enrollment, AND no documented plan to discontinue treatment&#xD;
               with oral anticoagulants for the expected duration of the trial.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Age &lt; 18 years&#xD;
  &#xD;
            2. Current left atrial appendage thrombus&#xD;
  &#xD;
            3. Prior left atrial appendage occlusion or removal (surgical or percutaneous)&#xD;
  &#xD;
            4. Prior percutaneous atrial septal defect or patent foramen ovale closure&#xD;
  &#xD;
            5. Prior atrial fibrillation ablation unless evidence of recurrent qualifying atrial&#xD;
               fibrillation present at least 30 days following ablation&#xD;
  &#xD;
            6. Planned atrial fibrillation ablation within 90 days of enrollment&#xD;
  &#xD;
            7. Individuals being treated with direct thrombin inhibitors&#xD;
  &#xD;
            8. Women of childbearing potential unless they agree to employ effective birth control&#xD;
               methods throughout the study&#xD;
  &#xD;
            9. Anticipated life-expectancy of &lt; 2 years&#xD;
  &#xD;
           10. Patient unable or willing to give informed consent&#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>Jeff Healey</last_name>
      <role>Principal Investigator</role>
      <affiliation>Hamilton Health Sciences Corporation</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tara McCready</last_name>
      <phone>905-521-2100</phone>
      <email>tara.mccready@phri.ca</email>
    </overall_contact>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 5, 2023</study_first_submitted>
    <study_first_submitted_qc>July 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 18, 2023</last_update_submitted>
    <last_update_submitted_qc>July 18, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 27, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>WATCHMAN</keyword>
    <keyword>Left Atrial Appendage (LAA)</keyword>
    <keyword>LAA Device</keyword>
    <keyword>Left Atrial Appendage Occlusion</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Ischemic Stroke</mesh_term>
      <mesh_term>Atrial Fibrillation</mesh_term>
      <mesh_term>Embolism</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/NCT05963698
  org study id: LAAOS-4
  nct id: NCT05963698
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  LAAOS-4 aims to determine if catheter-based endovascular left atrial appendage occlusion
        prevents ischemic stroke or systemic embolism in participants with atrial fibrillation, who
        remain at high risk of stroke, despite receiving ongoing treatment with oral anticoagulation.
  LAAOS-4 is a multicentre, prospective, open-label, randomized controlled trial with blinded
        assessment of endpoints (PROBE) to determine if catheter-based endovascular left atrial
        appendage occlusion prevents ischemic stroke or systemic embolism in participants with atrial
        fibrillation, who remain at high risk of stroke, despite receiving ongoing treatment with
        oral anticoagulation.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Randomized Controlled Trial
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  masking description: Events Adjudication Committee is blinded to intervention assignment.
  measure: Ischemic stroke or systemic embolism
  time frame: The study duration is event-driven. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: The primary efficacy variable is the time from randomization to first occurrence of any of the components of the composite outcome (adjudicated) over the duration of follow-up, including:
  Ischemic stroke (Strokes of undetermined etiology will be treated as ischemic stroke)
  Systemic embolism
  measure: All-cause stroke or systemic embolism
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Secondary efficacy outcomes will be evaluated in a hierarchical fashion only when the primary outcome meets statistical significance in the specified order:
  Time from randomization to first occurrence of all-cause stroke or systemic embolism
  measure: All-cause stroke, systemic embolism, or transient ischemic attack (TIA)
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Time from randomization to first occurrence of all-cause stroke, systemic embolism or transient ischemic attack (TIA)
  measure: Montreal Cognitive Assessment (MoCA) Score
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Proportion of participants with a decrease of two or more points on the MoCA score at either year 2 or end of study
  measure: New disabling ischemic strokes
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Time from randomization to first occurrence of disabling ischemic strokes with modified Rankin Score (mRS) >2, measured at 90 days post-stroke
  measure: Cardiovascular mortality
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Time from randomization to cardiovascular mortality
  measure: All-cause mortality
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Time from randomization to all-cause mortality
  measure: Non-procedural Major Bleeding
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Proportion of participants with non-procedural Major Bleeding (International Society on Thrombosis and Haemostasis (ISTH) definition; excluding WATCHMAN-related bleeding within 14 days of implant)
  measure: Hospitalization for any cause
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Time from randomization to first occurrence of hospitalization for any cause
  measure: Heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Time from randomization to first occurrence of heart failure hospitalization or emergency department/clinic visit for intensification of heart failure related therapy
  measure: Myocardial Infarction
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Time from randomization to first occurrence of Myocardial Infarction (4th Universal definition)
  measure: Device and procedural-related outcomes: Device-related thrombus
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Proportion of participants with device-related thrombus (thrombus formed on the surface of the WATCHMAN device)
  measure: Device and procedural-related outcomes: Incomplete left atrial appendage (LAA) closure
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Proportion of participants with incomplete LAA closure
  measure: Device and procedural-related outcomes: Peri-procedural major bleeding
  time frame: Will be evaluated once primary outcome meets statistical significance. The primary analysis will be performed through study completion, once 265 primary efficacy endpoint events have occurred (an estimated average follow-up of 4 years).
  description: Proportion of participants with peri-procedural major bleeding (ISTH definition; within 14 days following the procedure)
  arm group label: WATCHMAN device
  arm group type: Experimental
  description: Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
  arm group label: Standard Care
  arm group type: No Intervention
  description: Participants will receive local, standard medical care
  intervention type: Device
  intervention name: WATCHMAN device
  description: Participants will undergo endovascular left atrial appendage occlusion with the WATCHMAN device
  arm group label: WATCHMAN device
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Jeff Healey
  role: Principal Investigator
  affiliation: Hamilton Health Sciences Corporation
  last name: Tara McCready
  phone: 905-521-2100
  email: tara.mccready@phri.ca
  responsible party type: Sponsor
  mesh term: Ischemic Stroke
  mesh term: Atrial Fibrillation
  mesh term: Embolism
  sharing ipd: No