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/NCT05976685</url>
    </required_header>
    <id_info>
      <org_study_id>ELAPSE</org_study_id>
      <nct_id>NCT05976685</nct_id>
    </id_info>
    <brief_title>Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic Stroke Despite Anticoagulation Therapy</brief_title>
    <acronym>ELAPSE</acronym>
    <official_title>Early Closure of Left Atrial Appendage for Patients With Atrial Fibrillation and Ischemic StrokE Despite Anticoagulation Therapy</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Insel Gruppe AG, University Hospital Bern</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Insel Gruppe AG, University Hospital Bern</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>
        Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and cardioembolic&#xD;
        stroke due to AF is its major complication. Direct oral anticoagulants (DOAC) reduce the risk&#xD;
        of cardioembolism in patients with AF. Despite DOAC therapy, there is a significant residual&#xD;
        stroke risk of 1-2%/year. Recent data from the Swiss Stroke Registry found 38% of patients&#xD;
        with AF and ischemic stroke were on prior anticoagulant therapy (approximately 400 patients&#xD;
        per year in Switzerland). The investigators found in a prior observational study, that&#xD;
        patients with AF who have ischemic stroke despite anticoagulation are at increased risk of&#xD;
        having another ischemic stroke (HR 1.6; 95% confidence interval, CI 1.1-2.1). Combining&#xD;
        observational data from 11 international stroke centres, the investigators found that the&#xD;
        majority of ischemic strokes despite anticoagulation in patients with AF is &quot;breakthrough&quot;&#xD;
        cardioembolism (76% of patients) and only a minority of 24% is related to other causes&#xD;
        unrelated to AF. Optimal secondary prevention strategy is unknown. The investigators have&#xD;
        conducted two independent observational studies including together &gt;4000 patients but did not&#xD;
        identify any strategy (e.g. switch to different DOAC, additional antiplatelet therapy) that&#xD;
        seems superior. A recent randomized controlled trial on surgical occlusion of the left atrial&#xD;
        appendage (LAAO) found that LAAO may provide additional protection from ischaemic stroke in&#xD;
        addition to oral anticoagulation. Triggered by this finding, the investigators performed a&#xD;
        matched retrospective observational study and found that patients with AF and stroke despite&#xD;
        anticoagulation who received a combined mechanical-pharmacological therapy (DOAC therapy +&#xD;
        LAAO) had lower rates of adverse outcomes compared to those with DOAC therapy alone.&#xD;
        Therefore, the investigators hypothesize that in patients with AF and ischemic stroke despite&#xD;
        anticoagulant therapy, LAAO in addition to anticoagulation with a DOAC (and 3 months of&#xD;
        Clopidogrel after the intervention) is superior to DOAC therapy alone. The investigators&#xD;
        propose an international, multi-center randomized controlled two-arm trial to assess the&#xD;
        effect of LAAO in patients with AF suffering from strokes despite anticoagulation therapy and&#xD;
        without competing stroke etiology. The investigators will use the PROBE design with blinded&#xD;
        endpoint assessment. The investigators will enrol patients with non-valvular AF and a recent&#xD;
        ischemic stroke despite anticoagulation therapy at stroke onset. Patients will be randomized&#xD;
        1:1 to receive LAAO + DOAC therapy and 3 months of clopidogrel treatment (experimental arm)&#xD;
        or DOAC therapy alone (standard treatment arm). The primary endpoint is the first occurrence&#xD;
        of a composite outcome of recurrent ischemic stroke, systemic embolism and cardiovascular&#xD;
        death during follow-up. Secondary outcomes include individual components of the primary&#xD;
        composite outcome, safety outcomes (i.e. symptomatic intracranial haemorrhage, major&#xD;
        extracranial bleeding, serious device- or procedure-related complication), functional outcome&#xD;
        (modified Rankin Scale) and patient-oriented outcomes. The minimum follow-up is 6 months and&#xD;
        all patients will receive follow-ups every 6 months until end of study, the maximal follow-up&#xD;
        will be 48 months. Based on prior observational data from the investigators' group and others&#xD;
        (5 observational studies, &gt;5000 patients), the investigators estimate the proportion of&#xD;
        patients with the primary outcome in the standard treatment arm to be 18% in the first year&#xD;
        and 9% in the second year (=cumulative 27% after 2 years). A relative risk reduction of 40%&#xD;
        at 2 years would be clinically relevant. Based on these assumptions and a log-rank test, the&#xD;
        investigators would need 98 events for a power of 80% at an alpha-level of 5%. Assuming a&#xD;
        recruitment rate of 52, 118, 156 and 156 patients in years 1 to 4, an additional 6 months of&#xD;
        follow-up (mean follow-up time of 2.1 years) and a uniform drop-out rate of 7.5% per year,&#xD;
        482 patients would need to be enrolled. How to treat patients with an ischemic stroke despite&#xD;
        anticoagulation is a major yet unresolved clinical dilemma. This trial has the potential to&#xD;
        answer the question whether LAAO plus DOAC therapy is superior to current standard of care&#xD;
        for patients with AF who have ischemic stroke despite anticoagulation.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">January 1, 2024</start_date>
    <completion_date type="Anticipated">June 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">January 1, 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>Prevention</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Composite of recurrent ischemic stroke, systemic embolism, or cardiovascular death (whatever comes first).</measure>
      <time_frame>6 months</time_frame>
      <description>The primary endpoint is the first occurrence of a composite outcome of recurrent ischemic stroke, systemic embolism and cardiovascular death during follow-up. Stoke is defined as - New sudden focal neurological deficit of presumed cerebrovascular aetiology, occurring &gt; 24 hours after the index ischaemic stroke, that persisted beyond 24 hours and was not due to another identifiable cause 18 (transient ischaemic attack (TIA), defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia without cerebral infarction on imaging, is not judged as stroke) and/or by brain imaging (CT or MRI). Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion of an extremity or organ in absence of another likely mechanism (e.g. atherosclerosis, instrumentation or trauma). Cardiovascular death is defined as any death that is due to a vascular cause.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Recurrent ischemic stroke</measure>
      <time_frame>6 months</time_frame>
      <description>Stoke is defined as - New sudden focal neurological deficit of presumed cerebrovascular aetiology, occurring &gt; 24 hours after the index ischaemic stroke, that persisted beyond 24 hours and was not due to another identifiable cause 18 (transient ischaemic attack (TIA), defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia without cerebral infarction on imaging, is not judged as stroke) and/or by brain imaging (CT or MRI).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Systemic embolism</measure>
      <time_frame>6 months</time_frame>
      <description>Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion of an extremity or organ in absence of another likely mechanism (e.g. atherosclerosis, instrumentation or trauma).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cardiovascular death</measure>
      <time_frame>6 months</time_frame>
      <description>Cardiovascular death is defined as any death that is due to a vascular cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Symptomatic intracranial hemorrhage</measure>
      <time_frame>6 months</time_frame>
      <description>A relevant symptomatic intracranial haemorrhage, this includes subdural, epidural, subarachnoidal and intracerebral haemorrhage, is defined as haemorrhage that leads to a clinical worsening and hospitalisation and is assessed by the treating physician to be likely the cause of the new neurological symptom or the death. Intracerebral haemorrhage due to a trauma will not be considered.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major extracranial bleeding (ISTH)</measure>
      <time_frame>6 months</time_frame>
      <description>Definition released by the International Society of Thrombosis and Haemostasis (ISTH): clinically overt bleeding which was fatal or associated with any of the following: (a) a fall in hemoglobin level of 2 g/dL or more or documented transfusion of at least 2 units of packed red blood cells, (b) involvement of a critical anatomical site (intracranial, spinal, ocular, pericardial, articular, intramuscular with compartment syndrome, retroperitoneal).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Procedure-related death</measure>
      <time_frame>6 months</time_frame>
      <description>All-cause death within 30 days after randomization or during the index procedure hospitalization</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Serious device- or procedure-related complication</measure>
      <time_frame>6 months</time_frame>
      <description>7 days post-index procedure for device group subjects</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>All-cause hospitalization</measure>
      <time_frame>6 months</time_frame>
      <description>Any hospital stay of at least 24 hours</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cause-specific hospitalization</measure>
      <time_frame>6 months</time_frame>
      <description>Any hospital stay of at least 24 hours or which the primary admitting diagnosis was for heart failure, stroke, bleeding, atrial fibrillation, repeat AF-ablations, periprocedural complication, other cardiovascular causes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Global health</measure>
      <time_frame>6 months</time_frame>
      <description>Measured by PROMIS (Patient-reported Outcomes Measurement Information System) Adult Global Health; continuous</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Global safety</measure>
      <time_frame>6 months</time_frame>
      <description>Measured by FeelSaveScale; continuous</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Functional neurological outcome</measure>
      <time_frame>6 months</time_frame>
      <description>Modified Rankin Scale; ordinal</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">482</enrollment>
    <condition>Ischemic Stroke</condition>
    <condition>Atrial Fibrillation</condition>
    <arm_group>
      <arm_group_label>LAAO and DOAC therapy</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Left atrial appendage occlusion and three months of clopidogrel treatment, and therapy with direct oral anticoagulants</description>
    </arm_group>
    <arm_group>
      <arm_group_label>DOAC therapy only</arm_group_label>
      <arm_group_type>Other</arm_group_type>
      <description>Therapy with direct oral anticoagulants alone</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Left atrial appendage Occlusion and 3 months of Clopidogrel</intervention_name>
      <description>Left atrial appendage Occlusion and 3 months of Clopidogrel after the procedure. Choice of DOAC is at the discretion of the treating physician. The operators may use any of the two FDA (Food and Drug Administration) / CE (Conformite Europeenne) approved LAA occluder devices (Amulet or Watchman) for the LAAO procedure.</description>
      <arm_group_label>LAAO and DOAC therapy</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>DOAC</intervention_name>
      <description>Therapy with direct oral anticoagulants. Choice of DOAC is at the discretion of the treating physician.</description>
      <arm_group_label>DOAC therapy only</arm_group_label>
      <arm_group_label>LAAO and DOAC therapy</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Written informed consent according to country specific details&#xD;
  &#xD;
            -  Documented paroxysmal, persistent, or permanent non-valvular AF Recent (≤3 months)&#xD;
               imaging-proven ischemic stroke without intercurrent event since the stroke&#xD;
  &#xD;
            -  Active and ongoing anticoagulation therapy at stroke onset (i.e. not stopped/paused&#xD;
               for &gt;2 days within 1 week of stroke onset due to medical intervention or&#xD;
               non-adherence)&#xD;
  &#xD;
            -  Eligible for long-term DOAC therapy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Contraindications to DOAC therapy&#xD;
  &#xD;
            -  Life expectancy &lt;2 year according to the opinion of the investigator&#xD;
  &#xD;
            -  Age &lt;18 years and &gt; 85 years&#xD;
  &#xD;
            -  Known allergy against Clopidogrel&#xD;
  &#xD;
            -  Presence of at least one of the following potential competing stroke mechanisms:&#xD;
               ipsilateral high-grade intra-/extracranial artery stenosis, vasculitis, dissection,&#xD;
               endocarditis (all patients should undergo standardized work-up to exclude competing&#xD;
               non-AF stroke aetiology as recommended 22)&#xD;
  &#xD;
            -  LAAO not feasible according to operator based on the baseline TEE (Transesophageal&#xD;
               Echocardiography)&#xD;
  &#xD;
            -  Previous persistent foramen ovale or atrial septum defect closure&#xD;
  &#xD;
            -  Rheumatic heart disease&#xD;
  &#xD;
            -  Mechanical heart valve prosthesis&#xD;
  &#xD;
            -  Contraindications for transesophageal echocardiography (esophageal varices, esophageal&#xD;
               stricture, history of esophageal cancer).&#xD;
  &#xD;
            -  Surgical cardiac or non-cardiac surgical procedure within 30 days of randomization&#xD;
  &#xD;
            -  Enrolled in another IND (Investigational New Drug) and IDE (Investigational Device&#xD;
               Exemption) investigation of a cardiovascular device or an investigational drug&#xD;
  &#xD;
            -  Severely reduced LVEF (Left ventricular ejection fraction) &lt;30&#xD;
  &#xD;
            -  Severely reduced renal function (GFR&lt;30ml/min)&#xD;
  &#xD;
            -  NYHA (New York Heart Association) III-IV dyspnea&#xD;
  &#xD;
            -  Acute cardiac decompensation (NT proBNP &gt;5000)&#xD;
  &#xD;
            -  LAA is obliterated or surgically ligated&#xD;
  &#xD;
            -  Pregnancy or breastfeeding or planned pregnancy&#xD;
  &#xD;
            -  Exclusion criteria by TEE&#xD;
  &#xD;
            -  Pericardial effusion &gt;5mm&#xD;
  &#xD;
            -  Thrombus* in the LAAO&#xD;
  &#xD;
            -  LAA anatomy that cannot accommodate either a Watchman or an Amulet device according to&#xD;
               IFU (instructions for use) / the judgement of the operator&#xD;
  &#xD;
                 -  If a thrombus in the LAAO is found, anticoagulation with Warfarin (INR 2.5-3.5)&#xD;
                    may be started and if the thrombus disappears, the patient may be eligible for&#xD;
                    study enrollment.&#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>Lorenz Räber, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Cardiovascular Center, Inselspital Bern</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lorenz Räber, MD</last_name>
      <phone>+41316320929</phone>
      <email>Lorenz.Raeber@insel.ch</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>David Seiffge, MD</last_name>
      <phone>+41316640509</phone>
      <email>david.seiffge@insel.ch</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Stroke</keyword>
    <keyword>Direct oral anticoagulation</keyword>
    <keyword>Left atrial appendage occlusion</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>Cerebral Infarction</mesh_term>
      <mesh_term>Atrial Fibrillation</mesh_term>
      <mesh_term>Ischemia</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Clopidogrel</mesh_term>
    </intervention_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/NCT05976685
  org study id: ELAPSE
  nct id: NCT05976685
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and cardioembolic
        stroke due to AF is its major complication. Direct oral anticoagulants (DOAC) reduce the risk
        of cardioembolism in patients with AF. Despite DOAC therapy, there is a significant residual
        stroke risk of 1-2%/year. Recent data from the Swiss Stroke Registry found 38% of patients
        with AF and ischemic stroke were on prior anticoagulant therapy (approximately 400 patients
        per year in Switzerland). The investigators found in a prior observational study, that
        patients with AF who have ischemic stroke despite anticoagulation are at increased risk of
        having another ischemic stroke (HR 1.6; 95% confidence interval, CI 1.1-2.1). Combining
        observational data from 11 international stroke centres, the investigators found that the
        majority of ischemic strokes despite anticoagulation in patients with AF is "breakthrough"
        cardioembolism (76% of patients) and only a minority of 24% is related to other causes
        unrelated to AF. Optimal secondary prevention strategy is unknown. The investigators have
        conducted two independent observational studies including together >4000 patients but did not
        identify any strategy (e.g. switch to different DOAC, additional antiplatelet therapy) that
        seems superior. A recent randomized controlled trial on surgical occlusion of the left atrial
        appendage (LAAO) found that LAAO may provide additional protection from ischaemic stroke in
        addition to oral anticoagulation. Triggered by this finding, the investigators performed a
        matched retrospective observational study and found that patients with AF and stroke despite
        anticoagulation who received a combined mechanical-pharmacological therapy (DOAC therapy +
        LAAO) had lower rates of adverse outcomes compared to those with DOAC therapy alone.
        Therefore, the investigators hypothesize that in patients with AF and ischemic stroke despite
        anticoagulant therapy, LAAO in addition to anticoagulation with a DOAC (and 3 months of
        Clopidogrel after the intervention) is superior to DOAC therapy alone. The investigators
        propose an international, multi-center randomized controlled two-arm trial to assess the
        effect of LAAO in patients with AF suffering from strokes despite anticoagulation therapy and
        without competing stroke etiology. The investigators will use the PROBE design with blinded
        endpoint assessment. The investigators will enrol patients with non-valvular AF and a recent
        ischemic stroke despite anticoagulation therapy at stroke onset. Patients will be randomized
        1:1 to receive LAAO + DOAC therapy and 3 months of clopidogrel treatment (experimental arm)
        or DOAC therapy alone (standard treatment arm). The primary endpoint is the first occurrence
        of a composite outcome of recurrent ischemic stroke, systemic embolism and cardiovascular
        death during follow-up. Secondary outcomes include individual components of the primary
        composite outcome, safety outcomes (i.e. symptomatic intracranial haemorrhage, major
        extracranial bleeding, serious device- or procedure-related complication), functional outcome
        (modified Rankin Scale) and patient-oriented outcomes. The minimum follow-up is 6 months and
        all patients will receive follow-ups every 6 months until end of study, the maximal follow-up
        will be 48 months. Based on prior observational data from the investigators' group and others
        (5 observational studies, >5000 patients), the investigators estimate the proportion of
        patients with the primary outcome in the standard treatment arm to be 18% in the first year
        and 9% in the second year (=cumulative 27% after 2 years). A relative risk reduction of 40%
        at 2 years would be clinically relevant. Based on these assumptions and a log-rank test, the
        investigators would need 98 events for a power of 80% at an alpha-level of 5%. Assuming a
        recruitment rate of 52, 118, 156 and 156 patients in years 1 to 4, an additional 6 months of
        follow-up (mean follow-up time of 2.1 years) and a uniform drop-out rate of 7.5% per year,
        482 patients would need to be enrolled. How to treat patients with an ischemic stroke despite
        anticoagulation is a major yet unresolved clinical dilemma. This trial has the potential to
        answer the question whether LAAO plus DOAC therapy is superior to current standard of care
        for patients with AF who have ischemic stroke despite anticoagulation.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Prevention
  masking: Single (Outcomes Assessor)
  measure: Composite of recurrent ischemic stroke, systemic embolism, or cardiovascular death (whatever comes first).
  time frame: 6 months
  description: The primary endpoint is the first occurrence of a composite outcome of recurrent ischemic stroke, systemic embolism and cardiovascular death during follow-up. Stoke is defined as - New sudden focal neurological deficit of presumed cerebrovascular aetiology, occurring > 24 hours after the index ischaemic stroke, that persisted beyond 24 hours and was not due to another identifiable cause 18 (transient ischaemic attack (TIA), defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia without cerebral infarction on imaging, is not judged as stroke) and/or by brain imaging (CT or MRI). Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion of an extremity or organ in absence of another likely mechanism (e.g. atherosclerosis, instrumentation or trauma). Cardiovascular death is defined as any death that is due to a vascular cause.
  measure: Recurrent ischemic stroke
  time frame: 6 months
  description: Stoke is defined as - New sudden focal neurological deficit of presumed cerebrovascular aetiology, occurring > 24 hours after the index ischaemic stroke, that persisted beyond 24 hours and was not due to another identifiable cause 18 (transient ischaemic attack (TIA), defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischaemia without cerebral infarction on imaging, is not judged as stroke) and/or by brain imaging (CT or MRI).
  measure: Systemic embolism
  time frame: 6 months
  description: Systemic embolism is defined as abrupt vascular insufficiency associated with clinical or radiological evidence of arterial occlusion of an extremity or organ in absence of another likely mechanism (e.g. atherosclerosis, instrumentation or trauma).
  measure: Cardiovascular death
  time frame: 6 months
  description: Cardiovascular death is defined as any death that is due to a vascular cause.
  measure: Symptomatic intracranial hemorrhage
  time frame: 6 months
  description: A relevant symptomatic intracranial haemorrhage, this includes subdural, epidural, subarachnoidal and intracerebral haemorrhage, is defined as haemorrhage that leads to a clinical worsening and hospitalisation and is assessed by the treating physician to be likely the cause of the new neurological symptom or the death. Intracerebral haemorrhage due to a trauma will not be considered.
  measure: Major extracranial bleeding (ISTH)
  time frame: 6 months
  description: Definition released by the International Society of Thrombosis and Haemostasis (ISTH): clinically overt bleeding which was fatal or associated with any of the following: (a) a fall in hemoglobin level of 2 g/dL or more or documented transfusion of at least 2 units of packed red blood cells, (b) involvement of a critical anatomical site (intracranial, spinal, ocular, pericardial, articular, intramuscular with compartment syndrome, retroperitoneal).
  measure: Procedure-related death
  time frame: 6 months
  description: All-cause death within 30 days after randomization or during the index procedure hospitalization
  measure: Serious device- or procedure-related complication
  time frame: 6 months
  description: 7 days post-index procedure for device group subjects
  measure: All-cause hospitalization
  time frame: 6 months
  description: Any hospital stay of at least 24 hours
  measure: Cause-specific hospitalization
  time frame: 6 months
  description: Any hospital stay of at least 24 hours or which the primary admitting diagnosis was for heart failure, stroke, bleeding, atrial fibrillation, repeat AF-ablations, periprocedural complication, other cardiovascular causes
  measure: Global health
  time frame: 6 months
  description: Measured by PROMIS (Patient-reported Outcomes Measurement Information System) Adult Global Health; continuous
  measure: Global safety
  time frame: 6 months
  description: Measured by FeelSaveScale; continuous
  measure: Functional neurological outcome
  time frame: 6 months
  description: Modified Rankin Scale; ordinal
  arm group label: LAAO and DOAC therapy
  arm group type: Experimental
  description: Left atrial appendage occlusion and three months of clopidogrel treatment, and therapy with direct oral anticoagulants
  arm group label: DOAC therapy only
  arm group type: Other
  description: Therapy with direct oral anticoagulants alone
  intervention type: Procedure
  intervention name: Left atrial appendage Occlusion and 3 months of Clopidogrel
  description: Left atrial appendage Occlusion and 3 months of Clopidogrel after the procedure. Choice of DOAC is at the discretion of the treating physician. The operators may use any of the two FDA (Food and Drug Administration) / CE (Conformite Europeenne) approved LAA occluder devices (Amulet or Watchman) for the LAAO procedure.
  arm group label: LAAO and DOAC therapy
  intervention type: Drug
  intervention name: DOAC
  description: Therapy with direct oral anticoagulants. Choice of DOAC is at the discretion of the treating physician.
  arm group label: DOAC therapy only
  arm group label: LAAO and DOAC therapy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lorenz Räber, MD
  role: Principal Investigator
  affiliation: Cardiovascular Center, Inselspital Bern
  last name: Lorenz Räber, MD
  phone: +41316320929
  email: Lorenz.Raeber@insel.ch
  last name: David Seiffge, MD
  phone: +41316640509
  email: david.seiffge@insel.ch
  responsible party type: Sponsor
  mesh term: Stroke
  mesh term: Ischemic Stroke
  mesh term: Cerebral Infarction
  mesh term: Atrial Fibrillation
  mesh term: Ischemia
  mesh term: Clopidogrel
  sharing ipd: No