<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/NCT03819946</url>
  </required_header>
  <id_info>
    <org_study_id>IRAS253844</org_study_id>
    <nct_id>NCT03819946</nct_id>
  </id_info>
  <brief_title>Improving Oesophageal Protection During AF Ablation</brief_title>
  <acronym>IMPACT</acronym>
  <official_title>Oesophageal Protection: a Novel Approach to Improving the Safety of Catheter Ablation for Atrial Fibrillation.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>St. George's Hospital, London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Attune Medical</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>St. George's Hospital, London</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Catheter ablation is an established treatment for atrial fibrillation (AF). For those with&#xD;
      the more longstanding form of the condition and are graded as longstanding persistent AF,&#xD;
      catheter ablation techniques often involve an extensive ablative protocol. This often&#xD;
      includes application of ablation energy to the posterior left atrial wall. The left atrial&#xD;
      (LA) wall is only on average 5 millimetres away from the esophageal wall. It has been shown&#xD;
      that ablation to the posterior LA wall can cause thermal injury to the esophageal wall. Even&#xD;
      those that require pulmonary vein isolation only can be at risk of esophageal injury. This&#xD;
      injury can impact on patient symptoms as well as increase the risk of an atrio-esophageal&#xD;
      fistula being formed. Esophageal protection methods during catheter ablation for AF in&#xD;
      current practice is very limited and investigation towards improved approaches, in the form&#xD;
      of a randomized clinical trial is required.&#xD;
&#xD;
      The aim or purpose of this research project is to study the effect of esophageal cooling on&#xD;
      the incidence of esophageal thermal injury (endoscopy-graded esophageal epithelial lesions&#xD;
      and/or the presence of ablation-related gastroparesis with patient symptoms) compared to&#xD;
      controls, after a catheter ablation procedure for the treatment of AF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Overall design This is a randomized controlled trial with 1:1 randomization to study or&#xD;
      control group.&#xD;
&#xD;
      Treatment/intervention plan and rationale AF patients awaiting to have a planned catheter&#xD;
      ablation procedure as their treatment will be eligible for this study. If they participate,&#xD;
      there is a 1:1 randomization to study or control group.&#xD;
&#xD;
      The study group will have their catheter ablation procedure with utilization of esophageal&#xD;
      protection using the cooling tubing device (Attune Medical, Chicago IL). The cooling is&#xD;
      controlled by the procedural doctor, with temperatures set in the range of patient safety&#xD;
      (for example, cooling at 4 degrees). This device is already in use clinically albeit in a&#xD;
      different clinical setting. The device is currently used an intensive care setting to provide&#xD;
      whole body cooling. It is designed to be inserted into the esophagus. The temperature control&#xD;
      does not allow temperatures to go into the extremes, so preserving patient safety.&#xD;
&#xD;
      The control group will have their catheter ablation procedure using standard esophageal&#xD;
      protection methods, which is an esophageal temperature probe, to measure for any temperature&#xD;
      changes during application of ablation energy. If measured esophageal temperatures reach&#xD;
      beyond 38 degrees then ablation is halted in that area.&#xD;
&#xD;
      Follow up endoscopy assessment After the ablation procedure, a follow up upper GI endoscopy&#xD;
      test will be performed to review for any ablation-related thermal injury, by a group of&#xD;
      endoscopists who are 'blinded' to the randomization of the participant. The follow up&#xD;
      endoscopy test will be confirmed with the participant and the timing of this follow up test&#xD;
      is within 1 week of their catheter ablation procedure.&#xD;
&#xD;
      Clinic follow up The clinic follow up will remain exactly the same as standard care but at&#xD;
      the first clinic (this is 12 weeks or 3 months from the ablation procedure) we will review or&#xD;
      ask about any lingering gastro-esophageal symptoms and record this in a basic questionnaire&#xD;
      (the GerdQ questionnaire will be used).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 1, 2019</start_date>
  <completion_date type="Anticipated">February 1, 2020</completion_date>
  <primary_completion_date type="Anticipated">February 1, 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>This is a randomized clinical trial with 1:1 randomization to the study protocol or the control. The study group will have esophageal protection utilising the esophageal cooling device. The control group will have standard esophageal protection, using an esophageal temperature probe.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The endoscopists performing the follow up endoscopy test will be 'blinded' to the randomization of the trial participant, to minimise bias.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>• The incidence of catheter ablation related esophageal injury.</measure>
    <time_frame>7 days</time_frame>
    <description>The incidence of catheter ablation related esophageal injury will be assessed by endoscopic examination. Evidence of thermal injury or symptomatic gastroparesis will be recorded. The thermal injury scale is graded 0-6. 6 being the worst score indicating severe esophageal injury. Endoscopic evidence of gastroparesis is dictated by presence of significant food residue despite &gt;6 hours of fasting and must be correlated with new patient symptoms post-ablation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence of esophageal symptoms after catheter ablation treatment.</measure>
    <time_frame>3 months</time_frame>
    <description>During clinic assessment follow up, the participant will fill out a reflux symptoms questionnaire. This is called the GerdQ questionnaire (GerdQ stands for: gastro-esophageal reflux disease questionnaire). This is a scoring system of range 0-18, a score of 18 being the worst symptoms outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>• The incidence of major adverse outcomes (MACCE- major adverse cardiovascular cerebrovascular events) will be assessed.</measure>
    <time_frame>12 months</time_frame>
    <description>The major adverse events recorded includes the risk of cerebrovascular accident, transient ischaemic attacks (TIA) and myocardial infarction (MI). For each condition in this MACCE category- the recorded response will either be 'yes' or 'no' or 'positive' or 'negative'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Long-term success rate of the catheter ablation procedure as measured from freedom from the treated arrhythmia (atrial fibrillation/atrial tachycardias).</measure>
    <time_frame>12 months</time_frame>
    <description>During clinic follow up, Holter monitors (ambulatory ECG monitors) or implantable loop recorders will monitor for any recurrence of the treated arrhythmia. Any recurrence will be recorded to assess longterm success of the catheter ablation treatment (this is objectively measured at 12 months). The outcome response is recorded as either 'yes' or 'no'.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Esophageal Diseases</condition>
  <arm_group>
    <arm_group_label>Study Group- esophgeal cooling</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this study arm, the participants will have esophageal protection during their catheter ablation procedure, utilizing the esophageal cooling device (Attune Medical, Chicago, IL). During catheter ablation, the cooling device is set to cooling levels.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group- esophgeal temperature probe</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In this control group, the participants will have esophageal protection utilizing the standard method in current practice, which is an esophageal temperature probe. If recorded temperatures rise above 38 degrees during ablation, ablation treatment is halted in this region.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>esophageal cooling device (Attune Medical, Chicago, IL)</intervention_name>
    <description>The esophageal cooling device is a silicone soft tubing that is designed to be inserted into the esophagus. It is currently used clinically to provide whole body cooling or temperature control for intensive care patients (in medically induced coma or general anesthesia). The tubing is established but not been used in the clinical setting of catheter ablation for AF (which is performed under general anesthesia). During application of ablation energy to the posterior left atrial wall, the tubing is cooled to medium-low levels (25 degrees) and this is controlled by the operator.</description>
    <arm_group_label>Study Group- esophgeal cooling</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard esophageal temperature probe</intervention_name>
    <description>If the participant is randomized to the control group, then a standard esophageal protection method will be used during their catheter ablation procedure. This comprises of an esophageal temperature probe, inserted whilst the patient is under general anesthesia. If during application of ablation treatment to the posterior left atrial wall causes the esophageal temperature to rise above 38 degrees the ablation treatment is halted in this region. If ablation treatment is incomplete, re-application can be applied again cautiously if temperatures fall back to 37 degrees. Further temperature rise of over 38 degrees at the same region is a contra-indication to further ablation work here.</description>
    <arm_group_label>Control group- esophgeal temperature probe</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        • Any AF patient planned for a catheter ablation procedure or a left atrial ablation&#xD;
        protocol that puts them at risk of surrounding structural trauma, including oesophageal&#xD;
        injury.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients at the age extremities will not be approached for the study. (Paediatric&#xD;
             patients or young adults (&lt;aged 18) or older adults over the age of 85)&#xD;
&#xD;
          -  Patients having simple or non-left atrial ablation procedures not needing oesophageal&#xD;
             protection.&#xD;
&#xD;
          -  Patients at high risk of oesophageal bleeding e.g. oesophageal varices.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mark M Gallagher, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>St. George's Hospital NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sam Hollingworth, Bsc</last_name>
    <phone>+4420287256606</phone>
    <phone_ext>6606</phone_ext>
    <email>sahollin@sgul.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>St.George's Hospital</name>
      <address>
        <city>London</city>
        <zip>SW170QT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mark M Gallagher, MD</last_name>
      <phone>+442087253701</phone>
      <phone_ext>3701</phone_ext>
      <email>mark_m_gallagher@hotmail.com</email>
    </contact>
    <investigator>
      <last_name>Manav Sohal, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Abhay Bajpai, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Zia Zuberi, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anthony Li, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mark Norman, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Riyaz Kaba, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>January 20, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 29, 2019</study_first_posted>
  <last_update_submitted>December 30, 2019</last_update_submitted>
  <last_update_submitted_qc>December 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>St. George's Hospital, London</investigator_affiliation>
    <investigator_full_name>Dr. Mark M. Gallagher</investigator_full_name>
    <investigator_title>Clinical Lead for Cardiac Electrophysiology and Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Esophageal protection</keyword>
  <keyword>Ablation-related thermal injury</keyword>
  <keyword>Catheter ablation for AF</keyword>
  <keyword>Persistent AF ablation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esophageal Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>IPD will be anonymised and stored securely in the institutional secured electronic database network. During the study, the data will be available to site sub-investigators only.</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>April 27, 2022</submitted>
    <returned>January 26, 2023</returned>
  </pending_results>
  <!-- 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/NCT03819946
org study id: IRAS253844
nct id: NCT03819946
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Catheter ablation is an established treatment for atrial fibrillation (AF). For those with
      the more longstanding form of the condition and are graded as longstanding persistent AF,
      catheter ablation techniques often involve an extensive ablative protocol. This often
      includes application of ablation energy to the posterior left atrial wall. The left atrial
      (LA) wall is only on average 5 millimetres away from the esophageal wall. It has been shown
      that ablation to the posterior LA wall can cause thermal injury to the esophageal wall. Even
      those that require pulmonary vein isolation only can be at risk of esophageal injury. This
      injury can impact on patient symptoms as well as increase the risk of an atrio-esophageal
      fistula being formed. Esophageal protection methods during catheter ablation for AF in
      current practice is very limited and investigation towards improved approaches, in the form
      of a randomized clinical trial is required.

      The aim or purpose of this research project is to study the effect of esophageal cooling on
      the incidence of esophageal thermal injury (endoscopy-graded esophageal epithelial lesions
      and/or the presence of ablation-related gastroparesis with patient symptoms) compared to
      controls, after a catheter ablation procedure for the treatment of AF.
Overall design This is a randomized controlled trial with 1:1 randomization to study or
      control group.

      Treatment/intervention plan and rationale AF patients awaiting to have a planned catheter
      ablation procedure as their treatment will be eligible for this study. If they participate,
      there is a 1:1 randomization to study or control group.

      The study group will have their catheter ablation procedure with utilization of esophageal
      protection using the cooling tubing device (Attune Medical, Chicago IL). The cooling is
      controlled by the procedural doctor, with temperatures set in the range of patient safety
      (for example, cooling at 4 degrees). This device is already in use clinically albeit in a
      different clinical setting. The device is currently used an intensive care setting to provide
      whole body cooling. It is designed to be inserted into the esophagus. The temperature control
      does not allow temperatures to go into the extremes, so preserving patient safety.

      The control group will have their catheter ablation procedure using standard esophageal
      protection methods, which is an esophageal temperature probe, to measure for any temperature
      changes during application of ablation energy. If measured esophageal temperatures reach
      beyond 38 degrees then ablation is halted in that area.

      Follow up endoscopy assessment After the ablation procedure, a follow up upper GI endoscopy
      test will be performed to review for any ablation-related thermal injury, by a group of
      endoscopists who are 'blinded' to the randomization of the participant. The follow up
      endoscopy test will be confirmed with the participant and the timing of this follow up test
      is within 1 week of their catheter ablation procedure.

      Clinic follow up The clinic follow up will remain exactly the same as standard care but at
      the first clinic (this is 12 weeks or 3 months from the ablation procedure) we will review or
      ask about any lingering gastro-esophageal symptoms and record this in a basic questionnaire
      (the GerdQ questionnaire will be used).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a randomized clinical trial with 1:1 randomization to the study protocol or the control. The study group will have esophageal protection utilising the esophageal cooling device. The control group will have standard esophageal protection, using an esophageal temperature probe.
primary purpose: Prevention
masking: Single (Outcomes Assessor)
masking description: The endoscopists performing the follow up endoscopy test will be 'blinded' to the randomization of the trial participant, to minimise bias.
measure: • The incidence of catheter ablation related esophageal injury.
time frame: 7 days
description: The incidence of catheter ablation related esophageal injury will be assessed by endoscopic examination. Evidence of thermal injury or symptomatic gastroparesis will be recorded. The thermal injury scale is graded 0-6. 6 being the worst score indicating severe esophageal injury. Endoscopic evidence of gastroparesis is dictated by presence of significant food residue despite >6 hours of fasting and must be correlated with new patient symptoms post-ablation.
measure: The incidence of esophageal symptoms after catheter ablation treatment.
time frame: 3 months
description: During clinic assessment follow up, the participant will fill out a reflux symptoms questionnaire. This is called the GerdQ questionnaire (GerdQ stands for: gastro-esophageal reflux disease questionnaire). This is a scoring system of range 0-18, a score of 18 being the worst symptoms outcome.
measure: • The incidence of major adverse outcomes (MACCE- major adverse cardiovascular cerebrovascular events) will be assessed.
time frame: 12 months
description: The major adverse events recorded includes the risk of cerebrovascular accident, transient ischaemic attacks (TIA) and myocardial infarction (MI). For each condition in this MACCE category- the recorded response will either be 'yes' or 'no' or 'positive' or 'negative'.
measure: Long-term success rate of the catheter ablation procedure as measured from freedom from the treated arrhythmia (atrial fibrillation/atrial tachycardias).
time frame: 12 months
description: During clinic follow up, Holter monitors (ambulatory ECG monitors) or implantable loop recorders will monitor for any recurrence of the treated arrhythmia. Any recurrence will be recorded to assess longterm success of the catheter ablation treatment (this is objectively measured at 12 months). The outcome response is recorded as either 'yes' or 'no'.
arm group label: Study Group- esophgeal cooling
arm group type: Experimental
description: In this study arm, the participants will have esophageal protection during their catheter ablation procedure, utilizing the esophageal cooling device (Attune Medical, Chicago, IL). During catheter ablation, the cooling device is set to cooling levels.
arm group label: Control group- esophgeal temperature probe
arm group type: Active Comparator
description: In this control group, the participants will have esophageal protection utilizing the standard method in current practice, which is an esophageal temperature probe. If recorded temperatures rise above 38 degrees during ablation, ablation treatment is halted in this region.
intervention type: Device
intervention name: esophageal cooling device (Attune Medical, Chicago, IL)
description: The esophageal cooling device is a silicone soft tubing that is designed to be inserted into the esophagus. It is currently used clinically to provide whole body cooling or temperature control for intensive care patients (in medically induced coma or general anesthesia). The tubing is established but not been used in the clinical setting of catheter ablation for AF (which is performed under general anesthesia). During application of ablation energy to the posterior left atrial wall, the tubing is cooled to medium-low levels (25 degrees) and this is controlled by the operator.
arm group label: Study Group- esophgeal cooling
intervention type: Other
intervention name: Standard esophageal temperature probe
description: If the participant is randomized to the control group, then a standard esophageal protection method will be used during their catheter ablation procedure. This comprises of an esophageal temperature probe, inserted whilst the patient is under general anesthesia. If during application of ablation treatment to the posterior left atrial wall causes the esophageal temperature to rise above 38 degrees the ablation treatment is halted in this region. If ablation treatment is incomplete, re-application can be applied again cautiously if temperatures fall back to 37 degrees. Further temperature rise of over 38 degrees at the same region is a contra-indication to further ablation work here.
arm group label: Control group- esophgeal temperature probe
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Mark M Gallagher, MD
role: Principal Investigator
affiliation: St. George's Hospital NHS Foundation Trust
last name: Sam Hollingworth, Bsc
phone: +4420287256606
phone ext: 6606
email: sahollin@sgul.ac.uk
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: St. George's Hospital, London
investigator full name: Dr. Mark M. Gallagher
investigator title: Clinical Lead for Cardiac Electrophysiology and Principal Investigator
mesh term: Esophageal Diseases
sharing ipd: No
ipd description: IPD will be anonymised and stored securely in the institutional secured electronic database network. During the study, the data will be available to site sub-investigators only.
submitted: April 27, 2022
returned: January 26, 2023