<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/NCT03280121</url>
  </required_header>
  <id_info>
    <org_study_id>D031517</org_study_id>
    <nct_id>NCT03280121</nct_id>
  </id_info>
  <brief_title>Hernia Reduction Prior to Scheduled TIF Completion</brief_title>
  <acronym>HEURISTIC</acronym>
  <official_title>Hernia Reduction Prior to Scheduled TIF Completion- The HEURISTIC Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EndoGastric Solutions</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>EndoGastric Solutions</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_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hernia Reduction Prior to Scheduled TIF Completion using EsophyX ZR transoral device&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Evaluation of the relative merits, safety and effectiveness of the EsophyX ZR transoral&#xD;
      device in performing the standardized TIF 2.0 procedure preceded by laparoscopic Hiatal&#xD;
      Hernia repair in PPI-prescribed patients with persistent &quot;troublesome symptoms&quot; per the&#xD;
      Montreal consensus definition&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Slow enrollment and Covid-19&#xD;
  </why_stopped>
  <start_date type="Actual">October 5, 2018</start_date>
  <completion_date type="Actual">October 26, 2020</completion_date>
  <primary_completion_date type="Actual">April 30, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Prospective, investigator initiated, multicenter, non-randomized single arm, open label.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>pH Study</measure>
    <time_frame>48 hour monitoring period</time_frame>
    <description>Number of Participants with Normalization of Esophageal Acid Exposure. Normalization in esophageal acid exposure is defined by ≤ 5.3% of total time pH &lt; 4 in</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Change in Troublesome Symptoms From Baseline</measure>
    <time_frame>6 months</time_frame>
    <description>Per Montreal Consensus definition, troublesome symptoms are mild symptoms occurring two (2) or more days per week, or moderate/severe symptoms occurring more than 1 day per week</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With a Change in PPI Consumption From Baseline to 6 Months</measure>
    <time_frame>6 months</time_frame>
    <description>from daily use to occasional use or none at all.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Fundoplication</condition>
  <arm_group>
    <arm_group_label>TIF using EsophyX ZR transoral device</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transoral incisionless fundoplication which is a minimally invasive treatment for gastroesophageal reflux disease (GERD) using EsophyX ZR transoral device</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>EsophyX ZR transoral device</intervention_name>
    <description>TIF</description>
    <arm_group_label>TIF using EsophyX ZR transoral device</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-72 years&#xD;
&#xD;
          2. Dependent upon daily PPIs for &gt; 6 months. Daily use is defined as a double dose, or&#xD;
             full dose or half dose taken daily for more than 80% of the total number of days&#xD;
             during the proceeding evaluation period&#xD;
&#xD;
          3. Troublesome symptoms, specifically heartburn or regurgitation, while on optimized dose&#xD;
             of PPI's Troublesome heartburn or regurgitation symptoms are those which occur a&#xD;
             minimum of 2 days a week and are mild to severe in severity&#xD;
&#xD;
          4. Abnormal ambulatory (Bravo) pH study after off PPI therapy for 7 days, i.e. &gt; 5.3% of&#xD;
             the time with pH &lt; 4 in a 48-hour monitoring period&#xD;
&#xD;
          5. Normal or near normal esophageal motility (by Upper GI/ esophagram or manometry as&#xD;
             required)&#xD;
&#xD;
          6. Pre-enrollment Hiatal Hernia (axial height and transverse dimension) from &gt; 2 cm up to&#xD;
             4 cm inclusive.&#xD;
&#xD;
          7. Patient willing to cooperate with post-operative dietary recommendations and&#xD;
             assessment tests at the requisite follow-up visits&#xD;
&#xD;
          8. Signed informed consent Exclusion Criteria&#xD;
&#xD;
        1. BMI &gt; 35 2. Hiatal hernia ≤ 2 and &gt; 4 cm 3. Esophagitis Los Angeles grade C or D 4.&#xD;
        Esophageal ulcer 5. Esophageal stricture 6. Long-segment Barretts esophagus (Prague: C &gt; 1,&#xD;
        M &gt; 3) 7. Esophageal motility disorder 8. Pregnancy or plans for pregnancy in the next 12&#xD;
        months (in females) 9. Immunosuppression 10. ASA &gt; 2 11. Portal hypertension and/or varices&#xD;
        12. History of previous resective gastric or esophageal surgery, cervical spine fusion,&#xD;
        Zenker's diverticulum, esophageal epiphrenic diverticulum, achalasia, scleroderma or&#xD;
        dermatomyositis, eosinophilic esophagitis, or cirrhosis 13. Active gastro-duodenal ulcer&#xD;
        disease 14. Gastric outlet obstruction or stenosis 15. Severe gastroparesis or delayed&#xD;
        gastric emptying confirmed by solid-phase gastric emptying study if patient complains of&#xD;
        postprandial satiety during assessment 16. Coagulation disorders 17. Atypical symptoms&#xD;
        including gas bloat and dysphagia. 18. Any other presenting condition that in the opinion&#xD;
        of the investigator would not make participation in this study in the patient's best&#xD;
        interest.&#xD;
&#xD;
        Post Enrollment Exclusion -&#xD;
&#xD;
        1. Inability to repair Hiatal hernia with at least 2cm of intra-abdominal esophagus length.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>72 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael Murray, MD,FACS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Northern Nevada Medical Group</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Elkhart General Hospital</name>
      <address>
        <city>Elkhart</city>
        <state>Indiana</state>
        <zip>46514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aspirus Iron River Hospital</name>
      <address>
        <city>Iron River</city>
        <state>Michigan</state>
        <zip>49935</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northern Nevada Medical Center</name>
      <address>
        <city>Sparks</city>
        <state>Nevada</state>
        <zip>89434</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 9, 2017</study_first_submitted>
  <study_first_submitted_qc>September 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <results_first_submitted>November 13, 2020</results_first_submitted>
  <results_first_submitted_qc>December 12, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 7, 2021</results_first_posted>
  <last_update_submitted>January 25, 2021</last_update_submitted>
  <last_update_submitted_qc>January 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 10, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>transoral incisionless</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hernia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 19, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT03280121/Prot_SAP_ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>There were two sites that recruited patients. One was in Iron Mountain. Michigan and one in Sparks, Nevada. The procedures were done in hospitals. The recruitment was from August 18 2018 through February 2019. The study was closed by the sponsor due to slow enrollment.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>TIF Using EsophyX ZR Transoral Device</title>
          <description>Prospective, investigator initiated, multicenter, non-randomized single arm, open label</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>screen failure - 3 hernia too small and 1 pH too low</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>TIF Using EsophyX ZR Transoral Device</title>
          <description>Transoral incisionless fundoplication which is a minimally invasive treatment for gastroesophageal reflux disease (GERD) using EsophyX ZR transoral device&#xD;
EsophyX ZR transoral device: TIF</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62" lower_limit="36" upper_limit="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>pH Study</title>
        <description>Number of Participants with Normalization of Esophageal Acid Exposure. Normalization in esophageal acid exposure is defined by ≤ 5.3% of total time pH &lt; 4 in</description>
        <time_frame>48 hour monitoring period</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TIF Using EsophyX ZR Transoral Device-(SINGLE ARM)</title>
            <description>Transoral incisionless fundoplication which is a minimally invasive treatment for gastroesophageal reflux disease (GERD) using EsophyX ZR transoral device&#xD;
EsophyX ZR transoral device: TIF</description>
          </group>
        </group_list>
        <measure>
          <title>pH Study</title>
          <description>Number of Participants with Normalization of Esophageal Acid Exposure. Normalization in esophageal acid exposure is defined by ≤ 5.3% of total time pH &lt; 4 in</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Change in Troublesome Symptoms From Baseline</title>
        <description>Per Montreal Consensus definition, troublesome symptoms are mild symptoms occurring two (2) or more days per week, or moderate/severe symptoms occurring more than 1 day per week</description>
        <time_frame>6 months</time_frame>
        <population>The relatively small number of patients that were willing to come back for follow-up and assessment of outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>TIF Using EsophyX ZR Transoral Device-(SINGLE ARM)</title>
            <description>Transoral incisionless fundoplication which is a minimally invasive treatment for gastroesophageal reflux disease (GERD) using EsophyX ZR transoral device&#xD;
EsophyX ZR transoral device: TIF</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Change in Troublesome Symptoms From Baseline</title>
          <description>Per Montreal Consensus definition, troublesome symptoms are mild symptoms occurring two (2) or more days per week, or moderate/severe symptoms occurring more than 1 day per week</description>
          <population>The relatively small number of patients that were willing to come back for follow-up and assessment of outcome measure.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With a Change in PPI Consumption From Baseline to 6 Months</title>
        <description>from daily use to occasional use or none at all.</description>
        <time_frame>6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>TIF Using EsophyX ZR Transoral Device-(SINGLE ARM)</title>
            <description>Transoral incisionless fundoplication which is a minimally invasive treatment for gastroesophageal reflux disease (GERD) using EsophyX ZR transoral device&#xD;
EsophyX ZR transoral device: TIF</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With a Change in PPI Consumption From Baseline to 6 Months</title>
          <description>from daily use to occasional use or none at all.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>EsophyX ZR Transoral Device</title>
          <description>Transoral incisionless fundoplication which is a minimally invasive treatment for gastroesophageal reflux disease (GERD) using EsophyX ZR transoral device with Hiatal hernias ≤ 2 and &gt; 4 cm.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Bleeding, hematoma requiring intervention</sub_title>
                <description>The patient admitted, 10 days post op, for bleeding. Required 2 units of blood. Possibly procedure related but not device related. Husband stated she carried heavy boxes. IRB notified . The issue resolved on 11/17/18.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Cynthia Harris, Director of Clinical Trials</name_or_title>
      <organization>Daniel and Daniel Consulting, LLC</organization>
      <phone>775-392-2975</phone>
      <email>cindy@clinregconsult.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03280121
org study id: D031517
nct id: NCT03280121
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
Hernia Reduction Prior to Scheduled TIF Completion using EsophyX ZR transoral device
Evaluation of the relative merits, safety and effectiveness of the EsophyX ZR transoral
      device in performing the standardized TIF 2.0 procedure preceded by laparoscopic Hiatal
      Hernia repair in PPI-prescribed patients with persistent "troublesome symptoms" per the
      Montreal consensus definition
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective, investigator initiated, multicenter, non-randomized single arm, open label.
primary purpose: Treatment
masking: None (Open Label)
measure: pH Study
time frame: 48 hour monitoring period
description: Number of Participants with Normalization of Esophageal Acid Exposure. Normalization in esophageal acid exposure is defined by ≤ 5.3% of total time pH < 4 in
measure: Number of Participants With a Change in Troublesome Symptoms From Baseline
time frame: 6 months
description: Per Montreal Consensus definition, troublesome symptoms are mild symptoms occurring two (2) or more days per week, or moderate/severe symptoms occurring more than 1 day per week
measure: Number of Participants With a Change in PPI Consumption From Baseline to 6 Months
time frame: 6 months
description: from daily use to occasional use or none at all.
arm group label: TIF using EsophyX ZR transoral device
arm group type: Experimental
description: Transoral incisionless fundoplication which is a minimally invasive treatment for gastroesophageal reflux disease (GERD) using EsophyX ZR transoral device
intervention type: Device
intervention name: EsophyX ZR transoral device
description: TIF
arm group label: TIF using EsophyX ZR transoral device
criteria: 
gender: All
minimum age: 18 Years
maximum age: 72 Years
healthy volunteers: No
last name: Michael Murray, MD,FACS
role: Principal Investigator
affiliation: Northern Nevada Medical Group
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Hernia
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 