<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/NCT02979847</url>
  </required_header>
  <id_info>
    <org_study_id>2016AN0127</org_study_id>
    <nct_id>NCT02979847</nct_id>
  </id_info>
  <brief_title>Epicardial Approach in Recurred Atrial Fibrillation</brief_title>
  <acronym>EPIREAF</acronym>
  <official_title>Role of Epicardial Mapping and Ablation for Redo Procedure in Patients With Non-paroxysmal Atrial Fibrillation: a Prospective Randomized Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Korea University Anam Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Korea University Anam Hospital</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>
      We aimed to assess the benefit of epicardial mapping and ablation in patients with recurred&#xD;
      atrial tachyarrhythmias after single procedure for atrial fibrillation. We hypothesize that&#xD;
      both endocardial and epicardial approach is superior to only endocardial approach with&#xD;
      regards to clinical recurrence. Participants are randomized into a hybrid approach or an&#xD;
      endocardial approach.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Atrial electrical activity during atrial fibrillation depends on the distribution of&#xD;
      myocardial tissue. Circumferential and longitudinal muscular bundles are multi-level crossing&#xD;
      across the entire thickness of atrial wall. At radiofrequency catheter ablation for atrial&#xD;
      fibrillation, transmural lesions are important to reduce the arrhythmogenic substrates and to&#xD;
      prevent recurrence of scar-related atrial tachyarrhythmias.&#xD;
&#xD;
      Radiofrequency ablation applying electric current depends on impedance between patch and the&#xD;
      tip electrode of a catheter. Increased impedance results in increased tissue heating,&#xD;
      following an irreversible damage. However, overheating limits to create deep lesion formation&#xD;
      because an increased impedance impedes the energy delivery to tissue. Furthermore, prolonged&#xD;
      ablation time may result in severe complications, such as steam pop, cardiac perforation, and&#xD;
      char formation. Therefore, both endocardial and epicardial ablations may be more effective to&#xD;
      create a transmural lesion compared with only endocardial ablation.&#xD;
&#xD;
      Organized atrial tachycardia is common in patient who underwent ablation for atrial&#xD;
      fibrillation. Activation mapping for atrial tachycardia is critical for ablating an isthmus.&#xD;
      However, when the amplitude of endocardial potentials after previous ablations is decreased&#xD;
      as system does not detect, summation of data from endocardium may give us wrong information&#xD;
      about atrial tachycardia. Data from epicardial potential during tachycardia may be helpful to&#xD;
      terminate a tachycardia.&#xD;
&#xD;
      We aimed to assess the benefit of epicardial mapping and ablation in patients with recurred&#xD;
      atrial tachyarrhythmias after single procedure for atrial fibrillation. We hypothesize that&#xD;
      both endocardial and epicardial approach is superior to only endocardial approach with&#xD;
      regards to clinical recurrence. Participants are randomized into a hybrid approach or an&#xD;
      endocardial approach.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 29, 2016</start_date>
  <completion_date type="Actual">November 11, 2020</completion_date>
  <primary_completion_date type="Actual">May 29, 2020</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</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Freedom from AF/AT recurrence</measure>
    <time_frame>12 months</time_frame>
    <description>Freedom from sustained AF/AT recurrence Sustained AF/AT: sustained more than 30 sec documentation in clinical electrocardiography, Holter, event recorder</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Freedom from AF/AT recurrence without anti-arrhythmic drug use</measure>
    <time_frame>12 months</time_frame>
    <description>Freedom from sustained AF/AT recurrence without anti-arrhythmic drug use</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from AF recurrence</measure>
    <time_frame>12 months</time_frame>
    <description>Freedom from sustained AF recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Freedom from AT recurrence</measure>
    <time_frame>12 months</time_frame>
    <description>Freedom from sustained AT recurrence</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure Time</measure>
    <time_frame>Immediately after procedure</time_frame>
    <description>From skin to skin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fluoroscopic Time</measure>
    <time_frame>Immediately after procedure</time_frame>
    <description>Fluoroscopic Time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ablation Time</measure>
    <time_frame>Immediately after procedure</time_frame>
    <description>Ablation Time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure-related Acute Complications</measure>
    <time_frame>Immediately after procedure</time_frame>
    <description>Procedure-related Acute Complications</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Procedure-related Subacute Complications</measure>
    <time_frame>3 months after procedure</time_frame>
    <description>Procedure-related Subacute Complications</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Persistent Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>Treated</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>hybrid approach (epicardial and subsequent endocardial mappings and ablations)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>conventional endocardial approach</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>hybrid approach</intervention_name>
    <description>Before transseptal puncture, epicardial puncture is performed through subxyphoid approach. Atrial epicardial potentials are recorded using multi-electrode catheter, leading an activation map for atrial tachycardia and map for continuous fractionated atrial electrograms during atrial fibrillation. Endocardial potentials are also recorded in the same fashion. Procedural endpoint is a tachycardia termination or a noninducibility of tachycardia.</description>
    <arm_group_label>Treated</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>conventional endocardial approach</intervention_name>
    <description>Atrial endocardial potentials are recorded using multi-electrode catheter, leading an activation map for atrial tachycardia and map for continuous fractionated atrial electrograms during atrial fibrillation. Procedural endpoint is a tachycardia termination or a noninducibility of tachycardia.</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with persistent AF (AF episode lasting &gt; 7 days)&#xD;
&#xD;
          -  Patients with symptomatic AF that is refractory to at least one antiarrhythmic&#xD;
             medication&#xD;
&#xD;
          -  Patients with recurrent arrhythmia after prior catheter ablation&#xD;
&#xD;
          -  Patients undergoing a repeat ablation procedure for AF&#xD;
&#xD;
          -  At least one episode of AF must have been documented by ECG, Holter, loop recorder,&#xD;
             telemetry, trans telephonic monitoring (TTM), or implantable device within last 2&#xD;
             years of enrollment in this investigation&#xD;
&#xD;
          -  Patients must be able and willing to provide written informed consent to participate&#xD;
             in this investigation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with permanent AF;&#xD;
&#xD;
          -  Permanent AF will be defined as a sustained episode lasting more than 1 years and&#xD;
             sinus rhythm never be observed .&#xD;
&#xD;
          -  Patients for whom cardioversion or sinus rhythm will never be attempted/pursued;&#xD;
&#xD;
          -  Patients with AF felt to be secondary to an obvious reversible cause&#xD;
&#xD;
          -  Patients with contraindications to systemic anticoagulation with heparin or warfarin&#xD;
             or a direct thrombin inhibitor;&#xD;
&#xD;
          -  Moderate to severe valvular disease&#xD;
&#xD;
          -  Patients who are pregnant. Pregnancy will be assessed by patients informing the&#xD;
             physicians.&#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_official>
    <last_name>Young-Hoon Kim, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Korea University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Korea University Medical Center Anam hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <results_reference>
    <citation>Eckstein J, Zeemering S, Linz D, Maesen B, Verheule S, van Hunnik A, Crijns H, Allessie MA, Schotten U. Transmural conduction is the predominant mechanism of breakthrough during atrial fibrillation: evidence from simultaneous endo-epicardial high-density activation mapping. Circ Arrhythm Electrophysiol. 2013 Apr;6(2):334-41. doi: 10.1161/CIRCEP.113.000342. Epub 2013 Mar 19.</citation>
    <PMID>23512204</PMID>
  </results_reference>
  <results_reference>
    <citation>Lee G, Kumar S, Teh A, Madry A, Spence S, Larobina M, Goldblatt J, Brown R, Atkinson V, Moten S, Morton JB, Sanders P, Kistler PM, Kalman JM. Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wavefronts, and disorganized activity. Eur Heart J. 2014 Jan;35(2):86-97. doi: 10.1093/eurheartj/eht267. Epub 2013 Aug 8.</citation>
    <PMID>23935092</PMID>
  </results_reference>
  <results_reference>
    <citation>Lee G, Spence S, Teh A, Goldblatt J, Larobina M, Atkinson V, Brown R, Morton JB, Sanders P, Kistler PM, Kalman JM. High-density epicardial mapping of the pulmonary vein-left atrial junction in humans: insights into mechanisms of pulmonary vein arrhythmogenesis. Heart Rhythm. 2012 Feb;9(2):258-64. doi: 10.1016/j.hrthm.2011.09.010. Epub 2011 Sep 9.</citation>
    <PMID>21907170</PMID>
  </results_reference>
  <results_reference>
    <citation>Pak HN, Hwang C, Lim HE, Kim JS, Kim YH. Hybrid epicardial and endocardial ablation of persistent or permanent atrial fibrillation: a new approach for difficult cases. J Cardiovasc Electrophysiol. 2007 Sep;18(9):917-23. doi: 10.1111/j.1540-8167.2007.00882.x. Epub 2007 Jun 16.</citation>
    <PMID>17573836</PMID>
  </results_reference>
  <results_reference>
    <citation>Verheule S, Tuyls E, Gharaviri A, Hulsmans S, van Hunnik A, Kuiper M, Serroyen J, Zeemering S, Kuijpers NH, Schotten U. Loss of continuity in the thin epicardial layer because of endomysial fibrosis increases the complexity of atrial fibrillatory conduction. Circ Arrhythm Electrophysiol. 2013 Feb;6(1):202-11. doi: 10.1161/CIRCEP.112.975144. Epub 2013 Feb 6.</citation>
    <PMID>23390124</PMID>
  </results_reference>
  <results_reference>
    <citation>Eckstein J, Schotten U. Rotors and breakthroughs as three-dimensional perpetuators of atrial fibrillation. Cardiovasc Res. 2012 Apr 1;94(1):8-9. doi: 10.1093/cvr/cvs093. Epub 2012 Feb 13. No abstract available.</citation>
    <PMID>22331500</PMID>
  </results_reference>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>September 11, 2016</study_first_submitted>
  <study_first_submitted_qc>November 29, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 2, 2016</study_first_posted>
  <last_update_submitted>November 16, 2020</last_update_submitted>
  <last_update_submitted_qc>November 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Korea University Anam Hospital</investigator_affiliation>
    <investigator_full_name>Young-Hoon Kim, MD</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>persistent atrial fibrillation</keyword>
  <keyword>catheter ablation</keyword>
  <keyword>epicardial mapping and ablation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atrial Fibrillation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>The individual participant data is not available to share with other researchers.</ipd_description>
  </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/NCT02979847
org study id: 2016AN0127
nct id: NCT02979847
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
We aimed to assess the benefit of epicardial mapping and ablation in patients with recurred
      atrial tachyarrhythmias after single procedure for atrial fibrillation. We hypothesize that
      both endocardial and epicardial approach is superior to only endocardial approach with
      regards to clinical recurrence. Participants are randomized into a hybrid approach or an
      endocardial approach.
Atrial electrical activity during atrial fibrillation depends on the distribution of
      myocardial tissue. Circumferential and longitudinal muscular bundles are multi-level crossing
      across the entire thickness of atrial wall. At radiofrequency catheter ablation for atrial
      fibrillation, transmural lesions are important to reduce the arrhythmogenic substrates and to
      prevent recurrence of scar-related atrial tachyarrhythmias.

      Radiofrequency ablation applying electric current depends on impedance between patch and the
      tip electrode of a catheter. Increased impedance results in increased tissue heating,
      following an irreversible damage. However, overheating limits to create deep lesion formation
      because an increased impedance impedes the energy delivery to tissue. Furthermore, prolonged
      ablation time may result in severe complications, such as steam pop, cardiac perforation, and
      char formation. Therefore, both endocardial and epicardial ablations may be more effective to
      create a transmural lesion compared with only endocardial ablation.

      Organized atrial tachycardia is common in patient who underwent ablation for atrial
      fibrillation. Activation mapping for atrial tachycardia is critical for ablating an isthmus.
      However, when the amplitude of endocardial potentials after previous ablations is decreased
      as system does not detect, summation of data from endocardium may give us wrong information
      about atrial tachycardia. Data from epicardial potential during tachycardia may be helpful to
      terminate a tachycardia.

      We aimed to assess the benefit of epicardial mapping and ablation in patients with recurred
      atrial tachyarrhythmias after single procedure for atrial fibrillation. We hypothesize that
      both endocardial and epicardial approach is superior to only endocardial approach with
      regards to clinical recurrence. Participants are randomized into a hybrid approach or an
      endocardial approach.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Randomized
primary purpose: Treatment
masking: None (Open Label)
measure: Freedom from AF/AT recurrence
time frame: 12 months
description: Freedom from sustained AF/AT recurrence Sustained AF/AT: sustained more than 30 sec documentation in clinical electrocardiography, Holter, event recorder
measure: Freedom from AF/AT recurrence without anti-arrhythmic drug use
time frame: 12 months
description: Freedom from sustained AF/AT recurrence without anti-arrhythmic drug use
measure: Freedom from AF recurrence
time frame: 12 months
description: Freedom from sustained AF recurrence
measure: Freedom from AT recurrence
time frame: 12 months
description: Freedom from sustained AT recurrence
measure: Procedure Time
time frame: Immediately after procedure
description: From skin to skin
measure: Fluoroscopic Time
time frame: Immediately after procedure
description: Fluoroscopic Time
measure: Ablation Time
time frame: Immediately after procedure
description: Ablation Time
measure: Procedure-related Acute Complications
time frame: Immediately after procedure
description: Procedure-related Acute Complications
measure: Procedure-related Subacute Complications
time frame: 3 months after procedure
description: Procedure-related Subacute Complications
arm group label: Treated
arm group type: Experimental
description: hybrid approach (epicardial and subsequent endocardial mappings and ablations)
arm group label: Control
arm group type: Active Comparator
description: conventional endocardial approach
intervention type: Procedure
intervention name: hybrid approach
description: Before transseptal puncture, epicardial puncture is performed through subxyphoid approach. Atrial epicardial potentials are recorded using multi-electrode catheter, leading an activation map for atrial tachycardia and map for continuous fractionated atrial electrograms during atrial fibrillation. Endocardial potentials are also recorded in the same fashion. Procedural endpoint is a tachycardia termination or a noninducibility of tachycardia.
arm group label: Treated
intervention type: Procedure
intervention name: conventional endocardial approach
description: Atrial endocardial potentials are recorded using multi-electrode catheter, leading an activation map for atrial tachycardia and map for continuous fractionated atrial electrograms during atrial fibrillation. Procedural endpoint is a tachycardia termination or a noninducibility of tachycardia.
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Young-Hoon Kim, MD, PhD
role: Principal Investigator
affiliation: Korea University
facility: 
country: Korea, Republic of
citation: Eckstein J, Zeemering S, Linz D, Maesen B, Verheule S, van Hunnik A, Crijns H, Allessie MA, Schotten U. Transmural conduction is the predominant mechanism of breakthrough during atrial fibrillation: evidence from simultaneous endo-epicardial high-density activation mapping. Circ Arrhythm Electrophysiol. 2013 Apr;6(2):334-41. doi: 10.1161/CIRCEP.113.000342. Epub 2013 Mar 19.
PMID: 23512204
citation: Lee G, Kumar S, Teh A, Madry A, Spence S, Larobina M, Goldblatt J, Brown R, Atkinson V, Moten S, Morton JB, Sanders P, Kistler PM, Kalman JM. Epicardial wave mapping in human long-lasting persistent atrial fibrillation: transient rotational circuits, complex wavefronts, and disorganized activity. Eur Heart J. 2014 Jan;35(2):86-97. doi: 10.1093/eurheartj/eht267. Epub 2013 Aug 8.
PMID: 23935092
citation: Lee G, Spence S, Teh A, Goldblatt J, Larobina M, Atkinson V, Brown R, Morton JB, Sanders P, Kistler PM, Kalman JM. High-density epicardial mapping of the pulmonary vein-left atrial junction in humans: insights into mechanisms of pulmonary vein arrhythmogenesis. Heart Rhythm. 2012 Feb;9(2):258-64. doi: 10.1016/j.hrthm.2011.09.010. Epub 2011 Sep 9.
PMID: 21907170
citation: Pak HN, Hwang C, Lim HE, Kim JS, Kim YH. Hybrid epicardial and endocardial ablation of persistent or permanent atrial fibrillation: a new approach for difficult cases. J Cardiovasc Electrophysiol. 2007 Sep;18(9):917-23. doi: 10.1111/j.1540-8167.2007.00882.x. Epub 2007 Jun 16.
PMID: 17573836
citation: Verheule S, Tuyls E, Gharaviri A, Hulsmans S, van Hunnik A, Kuiper M, Serroyen J, Zeemering S, Kuijpers NH, Schotten U. Loss of continuity in the thin epicardial layer because of endomysial fibrosis increases the complexity of atrial fibrillatory conduction. Circ Arrhythm Electrophysiol. 2013 Feb;6(1):202-11. doi: 10.1161/CIRCEP.112.975144. Epub 2013 Feb 6.
PMID: 23390124
citation: Eckstein J, Schotten U. Rotors and breakthroughs as three-dimensional perpetuators of atrial fibrillation. Cardiovasc Res. 2012 Apr 1;94(1):8-9. doi: 10.1093/cvr/cvs093. Epub 2012 Feb 13. No abstract available.
PMID: 22331500
responsible party type: Principal Investigator
investigator affiliation: Korea University Anam Hospital
investigator full name: Young-Hoon Kim, MD
investigator title: Professor
mesh term: Atrial Fibrillation
sharing ipd: No
ipd description: The individual participant data is not available to share with other researchers.