<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/NCT04506814</url>
  </required_header>
  <id_info>
    <org_study_id>UR Re-ablation Paroxysmal AF</org_study_id>
    <nct_id>NCT04506814</nct_id>
  </id_info>
  <brief_title>Endocardial Vs Epicardial Ablation for Recurrent Paroxysmal AF</brief_title>
  <acronym>REPEAL-AF</acronym>
  <official_title>Comparison of Repeat Endocardial PVI Vs Epicardial Posterior Wall Isolation and LAA Clip Plus PVI for Recurrent Atrial Fibrillation After Prior PVI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Rochester</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Meshalkin Research Institute of Pathology of Circulation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Rochester</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is no current accepted and predictably effective ablative therapy for patients with&#xD;
      recurrent paroxysmal atrial fibrillation after prior pulmonary vein isolation (PVI). This&#xD;
      study will compare redo PVI with hybrid epicardial ablation incorporating posterior wall&#xD;
      isolation and LAA clip, and redo PVI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In these redo ablation patients, the ideal re-ablation strategy is unknown and many&#xD;
      techniques have been proposed but there is no consensus nor strong clinical trial data.&#xD;
&#xD;
      This treatment gap prompted the development of a combined minimally invasive epicardial and&#xD;
      endocardial ablation (&quot;Convergent&quot;) procedure. During the last decade, this &quot;hybrid&quot; approach&#xD;
      has garnered increasing acceptance in clinical practice, with several reports of promising&#xD;
      antiarrhythmic outcomes in challenging disease states, as well as modifications to maximize&#xD;
      safety and clinical outcomes. One key aspect of this approach is that it targets key drivers&#xD;
      of AF including the PVs but also the left atrial posterior wall (LAPW), combining endocardial&#xD;
      and epicardial energy delivery. The LAPW (or &quot;PV myocardium&quot;) shares similar embryological&#xD;
      origins and electrophysiological properties with the PVs, is predisposed to develop fibrosis,&#xD;
      and thus recognized as an important source of AF. Recently, the CONVERGE randomized clinical&#xD;
      trial demonstrated superiority of this hybrid approach compared to PVI in patients with&#xD;
      persistent AF.&#xD;
&#xD;
      The left atrial appendage (LAA) has also been designated as a potential important trigger&#xD;
      site of AF, and if isolated, may result in improved post-ablation AF outcomes. Although&#xD;
      catheter-based isolation is controversial due to the potential to increase the risk of&#xD;
      stroke, surgical exclusion of the LAA by placement of an occlusive clip has been suggested to&#xD;
      be both antiarrhythmic and anti-thrombotic. Thus it is proposed in this trial to incorporate&#xD;
      the LAA clip within the hybrid procedure.&#xD;
&#xD;
      Given the sheer volume of patients undergoing ablation of AF and the predictable necessity to&#xD;
      perform repeat ablation procedures on a portion of these patients, the need for a proven redo&#xD;
      ablation strategy is self-evident. The investigators thus propose a randomized clinical trial&#xD;
      to determine if there is incremental efficacy by performing LAPW/LAA isolation via a hybrid&#xD;
      approach in comparison to the conventional redo PVI alone in patients with paroxysmal AF.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">October 1, 2023</start_date>
  <completion_date type="Anticipated">December 1, 2025</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2025</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>Atrial fibrillation &gt; 30 secs</measure>
    <time_frame>At 1 year</time_frame>
    <description>Based on serial 7-day Holter recordings</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">162</enrollment>
  <condition>Recurrent Paroxysmal Atrial Fibrillation Despite Prior Pulmonary Vein Isolation</condition>
  <arm_group>
    <arm_group_label>Endocardial PVI</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Endocardial complete PVI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Epicardial Posterior Wall Isolation + LAA Exclusion + Endocardial PVI</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Minimally invasive surgical hybrid ablation using the convergent approach plus LAA exclusion using the clip</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Endocardial PVI</intervention_name>
    <description>Catheter based PVI</description>
    <arm_group_label>Endocardial PVI</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Epicardial Posterior Wall Isolation + LAA Exclusion + Endocardial PVI</intervention_name>
    <description>Minimally invasive PVI with posterior wall RF ablation + LAA clip + endocardial PVI</description>
    <arm_group_label>Epicardial Posterior Wall Isolation + LAA Exclusion + Endocardial PVI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Age &gt; 18 years&#xD;
&#xD;
          2. Symptomatic paroxysmal AF despite prior 1 or 2 PVI procedures within past 10 years&#xD;
             (paroxysmal AF lasting up to 7 days before spontaneous termination)&#xD;
&#xD;
          3. Eligible for referral for re-ablation based on current guidelines&#xD;
&#xD;
          4. LA diameter &lt; 6.0 cms on transthoracic echo&#xD;
&#xD;
          5. Willingness to comply with post-procedural follow-up requirements and to sign informed&#xD;
             consent&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Inability to undergo AF catheter ablation (e.g., presence of a left atrial thrombus,&#xD;
             contraindication to anticoagulation)&#xD;
&#xD;
          2. Prior history of open heart surgery&#xD;
&#xD;
          3. Prior history of pericarditis or pericardiocentesis&#xD;
&#xD;
          4. Prior history of stroke/TIA/systemic embolism&#xD;
&#xD;
          5. NYHA class IV congestive heart failure or LVEF &lt; 25%&#xD;
&#xD;
          6. Persistent or longstanding persistent AF (duration &gt; 1 year)&#xD;
&#xD;
          7. Coronary revascularization or valve surgery within 3 months&#xD;
&#xD;
          8. Prior valve surgery using a mechanical prosthesis&#xD;
&#xD;
          9. An estimated glomerular filtration rate (eGFR) &lt; 45mL/min/1.73m2, using the MDRD&#xD;
             calculation&#xD;
&#xD;
         10. Life expectancy &lt;1 year for any medical condition&#xD;
&#xD;
         11. AF due to reversible cause e.g. hyperthyroid state&#xD;
&#xD;
         12. Women who are pregnant or plan to become pregnant during the course of the trial**&#xD;
             Note: Women of childbearing potential must have a negative pregnancy test within 7&#xD;
             days prior to randomization.&#xD;
&#xD;
         13. Participation in other clinical trials that will affect the objectives of this study&#xD;
&#xD;
         14. History of non-compliance to medical therapy&#xD;
&#xD;
         15. Inability or unwillingness to provide informed consent&#xD;
&#xD;
         16. Resides at such a distance from the enrolling site so travel to follow-up visits would&#xD;
             be unusually difficult&#xD;
&#xD;
         17. Does not anticipate residing in the vicinity of the enrolling site for the duration of&#xD;
             the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jonathan Steinberg, MD</last_name>
    <phone>9734364155</phone>
    <email>jsteinberg@smgnj.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Rochester</name>
      <address>
        <city>Short Hills</city>
        <state>New Jersey</state>
        <zip>07078</zip>
        <country>United States</country>
      </address>
    </facility>
    <contact>
      <last_name>Jonathan Steinberg</last_name>
      <phone>973-436-4155</phone>
      <email>jsteinberg@smgnj.com</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 10, 2020</study_first_posted>
  <last_update_submitted>October 8, 2022</last_update_submitted>
  <last_update_submitted_qc>October 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Rochester</investigator_affiliation>
    <investigator_full_name>Jonathan Steinberg</investigator_full_name>
    <investigator_title>Collaborator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04506814
org study id: UR Re-ablation Paroxysmal AF
nct id: NCT04506814
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: Yes
There is no current accepted and predictably effective ablative therapy for patients with
      recurrent paroxysmal atrial fibrillation after prior pulmonary vein isolation (PVI). This
      study will compare redo PVI with hybrid epicardial ablation incorporating posterior wall
      isolation and LAA clip, and redo PVI.
In these redo ablation patients, the ideal re-ablation strategy is unknown and many
      techniques have been proposed but there is no consensus nor strong clinical trial data.

      This treatment gap prompted the development of a combined minimally invasive epicardial and
      endocardial ablation ("Convergent") procedure. During the last decade, this "hybrid" approach
      has garnered increasing acceptance in clinical practice, with several reports of promising
      antiarrhythmic outcomes in challenging disease states, as well as modifications to maximize
      safety and clinical outcomes. One key aspect of this approach is that it targets key drivers
      of AF including the PVs but also the left atrial posterior wall (LAPW), combining endocardial
      and epicardial energy delivery. The LAPW (or "PV myocardium") shares similar embryological
      origins and electrophysiological properties with the PVs, is predisposed to develop fibrosis,
      and thus recognized as an important source of AF. Recently, the CONVERGE randomized clinical
      trial demonstrated superiority of this hybrid approach compared to PVI in patients with
      persistent AF.

      The left atrial appendage (LAA) has also been designated as a potential important trigger
      site of AF, and if isolated, may result in improved post-ablation AF outcomes. Although
      catheter-based isolation is controversial due to the potential to increase the risk of
      stroke, surgical exclusion of the LAA by placement of an occlusive clip has been suggested to
      be both antiarrhythmic and anti-thrombotic. Thus it is proposed in this trial to incorporate
      the LAA clip within the hybrid procedure.

      Given the sheer volume of patients undergoing ablation of AF and the predictable necessity to
      perform repeat ablation procedures on a portion of these patients, the need for a proven redo
      ablation strategy is self-evident. The investigators thus propose a randomized clinical trial
      to determine if there is incremental efficacy by performing LAPW/LAA isolation via a hybrid
      approach in comparison to the conventional redo PVI alone in patients with paroxysmal AF.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Atrial fibrillation > 30 secs
time frame: At 1 year
description: Based on serial 7-day Holter recordings
arm group label: Endocardial PVI
arm group type: Active Comparator
description: Endocardial complete PVI
arm group label: Epicardial Posterior Wall Isolation + LAA Exclusion + Endocardial PVI
arm group type: Experimental
description: Minimally invasive surgical hybrid ablation using the convergent approach plus LAA exclusion using the clip
intervention type: Device
intervention name: Endocardial PVI
description: Catheter based PVI
arm group label: Endocardial PVI
intervention type: Device
intervention name: Epicardial Posterior Wall Isolation + LAA Exclusion + Endocardial PVI
description: Minimally invasive PVI with posterior wall RF ablation + LAA clip + endocardial PVI
arm group label: Epicardial Posterior Wall Isolation + LAA Exclusion + Endocardial PVI
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jonathan Steinberg, MD
phone: 9734364155
email: jsteinberg@smgnj.com
facility: 
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Rochester
investigator full name: Jonathan Steinberg
investigator title: Collaborator
mesh term: Atrial Fibrillation
mesh term: Recurrence
sharing ipd: No