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/NCT06042127</url>
    </required_header>
    <id_info>
      <org_study_id>2023 145-T</org_study_id>
      <nct_id>NCT06042127</nct_id>
    </id_info>
    <brief_title>POEM-F for Achalasia - International RCT</brief_title>
    <official_title>Per-oral Endoscopic Myotomy With Fundoplication for Achalasia - an International Multicenter Randomized Controlled Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chinese University of Hong Kong</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Deenanath Mangeshkar Hospital and Research Centre</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Johns Hopkins University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Northwestern University Feinberg School of Medicine</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Nanfang Hospital, Southern Medical University</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Asian Institute of Gastroenterology, India</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Post Graduate Institute of Medical Education and Research, Chandigarh</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Chinese University of Hong Kong</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>
        Per-oral endoscopic myotomy (POEM) has emerged as the endoscopic treatment of choice for&#xD;
        achalasia, offering comparable symptom relief with laparoscopic Heller's cardiomyotomy. The&#xD;
        main concern with POEM is the higher incidence of post-procedure gastroesophageal reflux&#xD;
        disease (GERD), occurring in up to 50-60% of patients. In order to reduce the risk of GERD,&#xD;
        endoscopic fundoplication has been developed as a novel procedure mimicking surgical anterior&#xD;
        partial fundoplication that can be performed in the same session as POEM (POEM-F). Case&#xD;
        series of POEM-F in patients with achalasia reported encouraging outcomes of low GERD rate of&#xD;
        ~12% at 1 year. Prospective comparative data between POEM-F and conventional POEM on&#xD;
        post-procedure GERD is current lacking. The investigators therefore designed an international&#xD;
        multicenter prospective randomized study to investigate the efficacy of POEM-F. We postulate&#xD;
        that POEM-F could reduce the incidence of post-procedure GERD when compared with conventional&#xD;
        POEM.&#xD;
  &#xD;
        This is an international multicenter randomized controlled trial conducted between high&#xD;
        volume expert centers from Hong Kong SAR, China, India and United States of America. Adult&#xD;
        patients with manometry confirmed achalasia would be randomised to undergo POEM-F or POEM.&#xD;
        The procedure would be performed by experts with vast experience in POEM. The primary outcome&#xD;
        is the incidence of post-procedure GERD at 1 year, defined by the updated Lyon consensus.&#xD;
        Secondary outcomes include technical and clinical success rates, adverse events, post-POEM&#xD;
        endoscopic and manometry findings as well as patients' symptom scores.&#xD;
  &#xD;
        Sample size calculation Based on existing pilot comparative data on POEM-F and POEM, it is&#xD;
        estimated that 84 patients would be required to demonstrate a difference in post-procedure&#xD;
        GERD of 45.0% to 16.6%, with 80% power and false positive rate of 0.05, accounting for 10%&#xD;
        loss to follow-up.&#xD;
  &#xD;
        Purpose and potential The current study proposal could demonstrate the superiority of POEM-F&#xD;
        over POEM in reducing post-procedural GERD. It would also demonstrate the safety and&#xD;
        reproducibility of the technique in expert centers across the globe. It could potentially&#xD;
        replace conventional POEM as the preferred minimally invasive endoscopic treatment for&#xD;
        achalasia.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Achalasia is the most common esophageal motility disorder worldwide, with an annual incidence&#xD;
        of 1.6 per 100'000 individual and prevalence of 10 per 100'000 population. The incidence of&#xD;
        achalasia has been dramatically rising over the past decade. A study conducted in Chicago&#xD;
        suggested that over the 10 years from 2004 to 2014, the incidence and prevalence of achalasia&#xD;
        were two- to threefold greater than estimates would have predicted. The likely explanation to&#xD;
        the rise in incidence is an increased awareness of this condition and widespread availability&#xD;
        of accurate diagnostic test with high resolution manometry. The cardinal features of&#xD;
        achalasia include failed relaxation of lower esophageal sphincter and absent esophageal&#xD;
        peristalsis. Owing to the benign nature of the disease, patients suffering from it would&#xD;
        experience longstanding debilitating symptoms of dysphagia, chest pain, regurgitation,&#xD;
        resulting in poor quality of life. In the past, laparoscopic Heller's cardiomyotomy with&#xD;
        partial fundoplication and endoscopic pneumatic dilatation were considered as treatment&#xD;
        options for achalasia.&#xD;
  &#xD;
        In the past 10 years, per-oral endoscopic myotomy (POEM) has emerged as the incisionless&#xD;
        minimally invasive endoscopic treatment of choice for achalasia. This Natural Orifice&#xD;
        Transluminal Endoscopic Surgical (NOTES) technique involves mucosal incision and creation of&#xD;
        a submucosal tunnel in the distal esophagus down to gastric cardia, followed by esophageal&#xD;
        and gastric myotomy. Since the procedure was first reported by Inoue H, et al in 2010, it has&#xD;
        seen worldwide acceptance as first-line therapy. POEM has been associated with excellent&#xD;
        relief of dysphagia and achalasia-related symptoms with a low and acceptable adverse event&#xD;
        rate of 0.5%. In a previous randomised controlled trial, POEM had a higher treatment success&#xD;
        rate than pneumatic dilatation. When compared with laparoscopic Heller's cardiomyotomy, POEM&#xD;
        was associated with at least similar treatment efficacy and a trend towards reduced short&#xD;
        term adverse event. POEM could perform even better than surgical myotomy in patients with&#xD;
        type III achalasia.&#xD;
  &#xD;
        The main limitation of POEM is the incidence of gastroesophageal reflux disease (GERD)&#xD;
        post-POEM. Kumbhari et al. looked at rates of GERD after POEM on patients who underwent&#xD;
        subsequent objective pH testing. A total of 282 patients were included in this analysis from&#xD;
        multiple centers in America, Asia, and Europe. About 58% of patients had objective evidence&#xD;
        of abnormal acid exposure, with 23% showing evidence of esophagitis. More concerning,&#xD;
        however, was that 60% of the patients with GERD were completely asymptomatic. This highlights&#xD;
        an important issue at hand that many patients, either related to the propensity of GERD to be&#xD;
        silent or the nature of achalasia to develop and insensate esophagus, do not report symptoms&#xD;
        while showing high rates of GERD. POEM has been found to be consistently associated with&#xD;
        higher rate of GERD than conventional Heller's cardiomyotomy or pneumatic dilatation across&#xD;
        multiple studies.&#xD;
  &#xD;
        Supported by evidence demonstrating the efficacy of partial fundoplication during Heller's&#xD;
        operation, there has been a significant interest in performing fundoplication after POEM&#xD;
        during the same session to prevent the development of post-POEM GERD. Inoue et al. pioneered&#xD;
        the technique of POEM-F that mimics the surgical Dor (anterior partial fundoplication)&#xD;
        procedure. In their pilot study, technical success was achieved in all 21 patients, and all&#xD;
        but one had an intact fundoplication wrap on upper endoscopy at a 1-month follow-up. Four&#xD;
        more studies conducted in Japan and India have reported good early outcomes with POEM-F&#xD;
        (Technical success of 85-100%) for achalasia. No severe adverse event has been reported in&#xD;
        these studies which reiterates the safety of this procedure. In the longest follow-up study&#xD;
        on POEM-F, GERD diagnosed by an abnormal esophageal acid exposure was seen in 11.1% of the 21&#xD;
        cases at one-year follow-up: comparable (8.8%) to a large meta-analysis of 4871 Heller's&#xD;
        cardiomyotomy with fundoplication procedures.&#xD;
  &#xD;
        To date, no prospective multicenter randomised study has been conducted to compare the&#xD;
        efficacy of POEM-F with conventional POEM in reducing post-procedure GERD. Therefore, in this&#xD;
        study, we aim to evaluate the of POEM-F in patients with achalasia through an international&#xD;
        multicenter randomized controlled trial.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 1, 2023</start_date>
    <completion_date type="Anticipated">October 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 31, 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>
      <intervention_model_description>Randomised controlled trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Post-procedure rate of gastroesophageal reflux</measure>
      <time_frame>1 year</time_frame>
      <description>Defined by updated Lyon 2.0 consensus as fulfilling one or more of the criteria:&#xD;
  Endoscopic erosive esophagitis, LA grade B or above&#xD;
  Long segment Barrett's esophagus&#xD;
  Peptic esophageal stricture&#xD;
  24-hour pH study with acid exposure time &gt;6% Both endoscopy and pH study to be performed with proton pump inhibitor stopped for 4 weeks</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Clinical success rate of procedure</measure>
      <time_frame>1 year</time_frame>
      <description>Post-treatment Eckhardt score &lt;=3</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse event of procedure</measure>
      <time_frame>30 day</time_frame>
      <description>frequency of severe adverse events with probable or definite attribution to the procedure based on the American Society of Gastrointestinal Endoscopy (ASGE) lexicon as well as Clavien Dindo classification</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Technical success rate of procedure</measure>
      <time_frame>1 day</time_frame>
      <description>Completing all steps of the intended procedure successfully in the same session</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Procedure time</measure>
      <time_frame>1 day</time_frame>
      <description>Procedure time of the intended procedure in minutes</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Erosive esophagitis on post-procedure endoscopy</measure>
      <time_frame>1 year</time_frame>
      <description>The presence of erosive esophagitis as well as the grading on post-procedure endoscopy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Fundoplication wrap integrity on post-procedure endoscopy</measure>
      <time_frame>1 year</time_frame>
      <description>Endoscopic appearance of fundoplication wrap on retroflexion in the stomach.&#xD;
  Intact - wrap is completely visualised&#xD;
  Indistinct - wrap is visualised but appears to be loosened&#xD;
  Absent - the wrap is completely not visible</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distensibility index on EndoFLIP, premyotomy</measure>
      <time_frame>During index procedure, before myotomy</time_frame>
      <description>Distensibility index (mm2/mmHg) using EndoFLIP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distensibility index on EndoFLIP, post myotomy</measure>
      <time_frame>During index procedure, after myotomy</time_frame>
      <description>Distensibility index (mm2/mmHg) using EndoFLIP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distensibility index on EndoFLIP, post fundoplication</measure>
      <time_frame>During index procedure, after fundoplication</time_frame>
      <description>Distensibility index (mm2/mmHg) using EndoFLIP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Distensibility index on EndoFLIP, on follow-up</measure>
      <time_frame>1 year</time_frame>
      <description>Distensibility index (mm2/mmHg) using EndoFLIP, at follow-up endoscopy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum diameter on EndoFLIP, premyotomy</measure>
      <time_frame>During index procedure, before myotomy</time_frame>
      <description>Maximum diameter (mm) on EndoFLIP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum diameter on EndoFLIP, post-myotomy</measure>
      <time_frame>During index procedure, after myotomy</time_frame>
      <description>Maximum diameter (mm) on EndoFLIP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum diameter on EndoFLIP, post-fundoplication</measure>
      <time_frame>During index procedure, after fundoplication</time_frame>
      <description>Maximum diameter (mm) on EndoFLIP</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum diameter on EndoFLIP, on follow-up</measure>
      <time_frame>1 year</time_frame>
      <description>Maximum diameter (mm) on EndoFLIP, at follow-up endoscopy</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GERD-HRQL score</measure>
      <time_frame>1 month, 3 month, 6 month and 1 year</time_frame>
      <description>Symptom and quality of life score relating to GERD</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GERD-RSI score</measure>
      <time_frame>1 month, 3 month, 6 month and 1 year</time_frame>
      <description>Symptom and quality of life score relating to GERD</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>GERD-Q score</measure>
      <time_frame>1 month, 3 month, 6 month and 1 year</time_frame>
      <description>Symptom and quality of life score relating to GERD</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Use of proton pump inhibitor post-procedure</measure>
      <time_frame>1 month, 3 month, 6 month, and 1 year</time_frame>
      <description>Number of participants who are on regular / as required / not on PPI</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">81</enrollment>
    <condition>Achalasia</condition>
    <arm_group>
      <arm_group_label>Per-oral endoscopic myotomy with fundoplication</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The detail of the procedure has been reported in the literature. After completion of myotomy as per conventional anterior POEM, a serosal incision would be made at the level of the GE junction below the diaphragmatic crus. The peritoneal cavity would then be entered and the anterior gastric wall could be identified. A detachable endoloop would be introduced alongside the endoscope with the guidance of endoscopic clip. Three to four clips would be applied to the anterior gastric fundus while additional 3-4 clips would be applied to the edge of the submucosal tunnel, all anchoring to the endoloop. Upon tightening of the endoloop the anterior fundus would be approximated to the esophagogastric junction and thus completing the partial anterior fundoplication. Abdominal paracentesis to treat capnoperitoneum would be performed as required based on patient's clinical condition.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Conventional POEM</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Conventional per-oral endoscopic myotomy An anterior POEM would be performed per usual manner described in the literature. The procedure would be performed under general anaesthesia by expert endoscopists with at least 50 case experience of conventional POEM and 5 cases experience of POEM-F. The requirement of POEM experience is based on a recent multicenter study of learning curve by Fujiyoshi Y, et al. The procedure would follow the current recommendations from expert panel in reducing GER, including avoidance of excessive gastric myotomy and preservation of the sling fibers are the gastric cardia. The length of the esophageal and gastric myotomy is standardized at 5cm and 2cm respectively</description>
    </arm_group>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>POEM-F</intervention_name>
      <description>POEM-F would be performed as described in the arms section</description>
      <arm_group_label>Per-oral endoscopic myotomy with fundoplication</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Conventional POEM</intervention_name>
      <description>Anterior POEM performed as described in the arms section</description>
      <arm_group_label>Conventional POEM</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion criteria:&#xD;
  &#xD;
            1. Adult patient (age ≥18 and ≤65 years-old) and with symptomatic achalasia type I or II.&#xD;
  &#xD;
            2. Capability of understanding and complying with the study requirements, including&#xD;
               filling the Eckardt Score, GERD-HRQL and RSI questionnaire and signing the informed&#xD;
               consent form.&#xD;
  &#xD;
            3. Patients with achalasia type I, II or III who are one of the following:&#xD;
  &#xD;
                 -  Treatment naïve, or&#xD;
  &#xD;
                 -  Failed prior through-the-scope balloon dilation, Savary or pneumatic dilation&#xD;
  &#xD;
          Exclusion criteria:&#xD;
  &#xD;
            1. Patients unable or unwilling to provide consent.&#xD;
  &#xD;
            2. Previous esophageal or gastric surgery.&#xD;
  &#xD;
            3. Prior achalasia treatment including Heller myotomy, POEM.&#xD;
  &#xD;
            4. Sigmoid achalasia, or significant esophageal dilatation &gt;6cm in lower esophagus&#xD;
  &#xD;
            5. Disrupted mucosal integrity at the distal esophagus, eg. Ulcer, fibrotic scars etc&#xD;
  &#xD;
            6. Patients with large hiatal hernias (axial length &gt; 2 cm and Hill grade &gt;2).&#xD;
  &#xD;
            7. Patients with significant cardiorespiratory comorbidities which may limit their&#xD;
               ability to undertake general anesthesia for the procedure, including ASA grade III or&#xD;
               above.&#xD;
  &#xD;
            8. Patients with obesity (Body Mass Index (BMI) ≥ 30).&#xD;
  &#xD;
            9. Pregnant women or those planning pregnancy or breastfeeding women.&#xD;
  &#xD;
           10. Uncorrectable coagulopathy defined by international normalized ratio (INR) &gt; 1.5 or&#xD;
               platelet count &lt; 50000/µl.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Hon Chi Yip, FRCSEd</last_name>
      <role>Principal Investigator</role>
      <affiliation>Chinese University of Hong Kong</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Hon Chi Yip, FRCSEd</last_name>
      <phone>35052627</phone>
      <email>hcyip@surgery.cuhk.edu.hk</email>
    </overall_contact>
    <location>
      <facility>
        <name>Johns Hopkins Hospital</name>
        <address>
          <city>Baltimore</city>
          <state>Maryland</state>
          <zip>21287</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Mouen Khashab</last_name>
        <email>mkhasha1@jhmi.edu</email>
      </contact>
      <investigator>
        <last_name>Farimah Fayyaz</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Mouen Khashab</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Nanfang Hospital, Southern Medical University</name>
        <address>
          <city>Guangzhou</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Xiaobei Luo</last_name>
        <email>luoxiaobei63@126.com</email>
      </contact>
      <investigator>
        <last_name>Xiaobei Luo</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>The Chinese University of Hong Kong</name>
        <address>
          <city>Hong Kong</city>
          <country>Hong Kong</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Post Graduate Institute of Medical Education and Research</name>
        <address>
          <city>Chandigarh</city>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>Jayanta Samanta</last_name>
        <email>dj_samanta@yahoo.co.in</email>
      </contact>
      <investigator>
        <last_name>Jayanta Samanta</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Asian Institute of Gastroenterology</name>
        <address>
          <city>Hyderabad</city>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>Mohan Ramchandani</last_name>
        <email>ramchandanimohan@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Mohan Ramchandani</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Nabi Zaheer</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Baldota Institute of Digestive Sciences</name>
        <address>
          <city>Mumbai</city>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>Amit Maydeo</last_name>
        <email>amitmaydeo@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Amit Maydeo</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Gaurav Patil</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Amat Nagesh</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location>
      <facility>
        <name>Deenanath Mangeshkar Hospital &amp; Research Center</name>
        <address>
          <city>Pune</city>
          <country>India</country>
        </address>
      </facility>
      <contact>
        <last_name>Amol Bapaye</last_name>
        <email>amolbapaye@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Amol Bapaye</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
      <country>Hong Kong</country>
      <country>India</country>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>September 6, 2023</study_first_submitted>
    <study_first_submitted_qc>September 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 18, 2023</study_first_posted>
    <last_update_submitted>September 11, 2023</last_update_submitted>
    <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Chinese University of Hong Kong</investigator_affiliation>
      <investigator_full_name>Hon Chi Yip</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>POEM</keyword>
    <keyword>Fundoplication</keyword>
    <keyword>GERD</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Esophageal Achalasia</mesh_term>
    </condition_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/NCT06042127
  org study id: 2023 145-T
  nct id: NCT06042127
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  Per-oral endoscopic myotomy (POEM) has emerged as the endoscopic treatment of choice for
        achalasia, offering comparable symptom relief with laparoscopic Heller's cardiomyotomy. The
        main concern with POEM is the higher incidence of post-procedure gastroesophageal reflux
        disease (GERD), occurring in up to 50-60% of patients. In order to reduce the risk of GERD,
        endoscopic fundoplication has been developed as a novel procedure mimicking surgical anterior
        partial fundoplication that can be performed in the same session as POEM (POEM-F). Case
        series of POEM-F in patients with achalasia reported encouraging outcomes of low GERD rate of
        ~12% at 1 year. Prospective comparative data between POEM-F and conventional POEM on
        post-procedure GERD is current lacking. The investigators therefore designed an international
        multicenter prospective randomized study to investigate the efficacy of POEM-F. We postulate
        that POEM-F could reduce the incidence of post-procedure GERD when compared with conventional
        POEM.
  
        This is an international multicenter randomized controlled trial conducted between high
        volume expert centers from Hong Kong SAR, China, India and United States of America. Adult
        patients with manometry confirmed achalasia would be randomised to undergo POEM-F or POEM.
        The procedure would be performed by experts with vast experience in POEM. The primary outcome
        is the incidence of post-procedure GERD at 1 year, defined by the updated Lyon consensus.
        Secondary outcomes include technical and clinical success rates, adverse events, post-POEM
        endoscopic and manometry findings as well as patients' symptom scores.
  
        Sample size calculation Based on existing pilot comparative data on POEM-F and POEM, it is
        estimated that 84 patients would be required to demonstrate a difference in post-procedure
        GERD of 45.0% to 16.6%, with 80% power and false positive rate of 0.05, accounting for 10%
        loss to follow-up.
  
        Purpose and potential The current study proposal could demonstrate the superiority of POEM-F
        over POEM in reducing post-procedural GERD. It would also demonstrate the safety and
        reproducibility of the technique in expert centers across the globe. It could potentially
        replace conventional POEM as the preferred minimally invasive endoscopic treatment for
        achalasia.
  Achalasia is the most common esophageal motility disorder worldwide, with an annual incidence
        of 1.6 per 100'000 individual and prevalence of 10 per 100'000 population. The incidence of
        achalasia has been dramatically rising over the past decade. A study conducted in Chicago
        suggested that over the 10 years from 2004 to 2014, the incidence and prevalence of achalasia
        were two- to threefold greater than estimates would have predicted. The likely explanation to
        the rise in incidence is an increased awareness of this condition and widespread availability
        of accurate diagnostic test with high resolution manometry. The cardinal features of
        achalasia include failed relaxation of lower esophageal sphincter and absent esophageal
        peristalsis. Owing to the benign nature of the disease, patients suffering from it would
        experience longstanding debilitating symptoms of dysphagia, chest pain, regurgitation,
        resulting in poor quality of life. In the past, laparoscopic Heller's cardiomyotomy with
        partial fundoplication and endoscopic pneumatic dilatation were considered as treatment
        options for achalasia.
  
        In the past 10 years, per-oral endoscopic myotomy (POEM) has emerged as the incisionless
        minimally invasive endoscopic treatment of choice for achalasia. This Natural Orifice
        Transluminal Endoscopic Surgical (NOTES) technique involves mucosal incision and creation of
        a submucosal tunnel in the distal esophagus down to gastric cardia, followed by esophageal
        and gastric myotomy. Since the procedure was first reported by Inoue H, et al in 2010, it has
        seen worldwide acceptance as first-line therapy. POEM has been associated with excellent
        relief of dysphagia and achalasia-related symptoms with a low and acceptable adverse event
        rate of 0.5%. In a previous randomised controlled trial, POEM had a higher treatment success
        rate than pneumatic dilatation. When compared with laparoscopic Heller's cardiomyotomy, POEM
        was associated with at least similar treatment efficacy and a trend towards reduced short
        term adverse event. POEM could perform even better than surgical myotomy in patients with
        type III achalasia.
  
        The main limitation of POEM is the incidence of gastroesophageal reflux disease (GERD)
        post-POEM. Kumbhari et al. looked at rates of GERD after POEM on patients who underwent
        subsequent objective pH testing. A total of 282 patients were included in this analysis from
        multiple centers in America, Asia, and Europe. About 58% of patients had objective evidence
        of abnormal acid exposure, with 23% showing evidence of esophagitis. More concerning,
        however, was that 60% of the patients with GERD were completely asymptomatic. This highlights
        an important issue at hand that many patients, either related to the propensity of GERD to be
        silent or the nature of achalasia to develop and insensate esophagus, do not report symptoms
        while showing high rates of GERD. POEM has been found to be consistently associated with
        higher rate of GERD than conventional Heller's cardiomyotomy or pneumatic dilatation across
        multiple studies.
  
        Supported by evidence demonstrating the efficacy of partial fundoplication during Heller's
        operation, there has been a significant interest in performing fundoplication after POEM
        during the same session to prevent the development of post-POEM GERD. Inoue et al. pioneered
        the technique of POEM-F that mimics the surgical Dor (anterior partial fundoplication)
        procedure. In their pilot study, technical success was achieved in all 21 patients, and all
        but one had an intact fundoplication wrap on upper endoscopy at a 1-month follow-up. Four
        more studies conducted in Japan and India have reported good early outcomes with POEM-F
        (Technical success of 85-100%) for achalasia. No severe adverse event has been reported in
        these studies which reiterates the safety of this procedure. In the longest follow-up study
        on POEM-F, GERD diagnosed by an abnormal esophageal acid exposure was seen in 11.1% of the 21
        cases at one-year follow-up: comparable (8.8%) to a large meta-analysis of 4871 Heller's
        cardiomyotomy with fundoplication procedures.
  
        To date, no prospective multicenter randomised study has been conducted to compare the
        efficacy of POEM-F with conventional POEM in reducing post-procedure GERD. Therefore, in this
        study, we aim to evaluate the of POEM-F in patients with achalasia through an international
        multicenter randomized controlled trial.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Randomised controlled trial
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Post-procedure rate of gastroesophageal reflux
  time frame: 1 year
  description: Defined by updated Lyon 2.0 consensus as fulfilling one or more of the criteria:
  Endoscopic erosive esophagitis, LA grade B or above
  Long segment Barrett's esophagus
  Peptic esophageal stricture
  24-hour pH study with acid exposure time >6% Both endoscopy and pH study to be performed with proton pump inhibitor stopped for 4 weeks
  measure: Clinical success rate of procedure
  time frame: 1 year
  description: Post-treatment Eckhardt score <=3
  measure: Adverse event of procedure
  time frame: 30 day
  description: frequency of severe adverse events with probable or definite attribution to the procedure based on the American Society of Gastrointestinal Endoscopy (ASGE) lexicon as well as Clavien Dindo classification
  measure: Technical success rate of procedure
  time frame: 1 day
  description: Completing all steps of the intended procedure successfully in the same session
  measure: Procedure time
  time frame: 1 day
  description: Procedure time of the intended procedure in minutes
  measure: Erosive esophagitis on post-procedure endoscopy
  time frame: 1 year
  description: The presence of erosive esophagitis as well as the grading on post-procedure endoscopy
  measure: Fundoplication wrap integrity on post-procedure endoscopy
  time frame: 1 year
  description: Endoscopic appearance of fundoplication wrap on retroflexion in the stomach.
  Intact - wrap is completely visualised
  Indistinct - wrap is visualised but appears to be loosened
  Absent - the wrap is completely not visible
  measure: Distensibility index on EndoFLIP, premyotomy
  time frame: During index procedure, before myotomy
  description: Distensibility index (mm2/mmHg) using EndoFLIP
  measure: Distensibility index on EndoFLIP, post myotomy
  time frame: During index procedure, after myotomy
  description: Distensibility index (mm2/mmHg) using EndoFLIP
  measure: Distensibility index on EndoFLIP, post fundoplication
  time frame: During index procedure, after fundoplication
  description: Distensibility index (mm2/mmHg) using EndoFLIP
  measure: Distensibility index on EndoFLIP, on follow-up
  time frame: 1 year
  description: Distensibility index (mm2/mmHg) using EndoFLIP, at follow-up endoscopy
  measure: Maximum diameter on EndoFLIP, premyotomy
  time frame: During index procedure, before myotomy
  description: Maximum diameter (mm) on EndoFLIP
  measure: Maximum diameter on EndoFLIP, post-myotomy
  time frame: During index procedure, after myotomy
  description: Maximum diameter (mm) on EndoFLIP
  measure: Maximum diameter on EndoFLIP, post-fundoplication
  time frame: During index procedure, after fundoplication
  description: Maximum diameter (mm) on EndoFLIP
  measure: Maximum diameter on EndoFLIP, on follow-up
  time frame: 1 year
  description: Maximum diameter (mm) on EndoFLIP, at follow-up endoscopy
  measure: GERD-HRQL score
  time frame: 1 month, 3 month, 6 month and 1 year
  description: Symptom and quality of life score relating to GERD
  measure: GERD-RSI score
  time frame: 1 month, 3 month, 6 month and 1 year
  description: Symptom and quality of life score relating to GERD
  measure: GERD-Q score
  time frame: 1 month, 3 month, 6 month and 1 year
  description: Symptom and quality of life score relating to GERD
  measure: Use of proton pump inhibitor post-procedure
  time frame: 1 month, 3 month, 6 month, and 1 year
  description: Number of participants who are on regular / as required / not on PPI
  arm group label: Per-oral endoscopic myotomy with fundoplication
  arm group type: Experimental
  description: The detail of the procedure has been reported in the literature. After completion of myotomy as per conventional anterior POEM, a serosal incision would be made at the level of the GE junction below the diaphragmatic crus. The peritoneal cavity would then be entered and the anterior gastric wall could be identified. A detachable endoloop would be introduced alongside the endoscope with the guidance of endoscopic clip. Three to four clips would be applied to the anterior gastric fundus while additional 3-4 clips would be applied to the edge of the submucosal tunnel, all anchoring to the endoloop. Upon tightening of the endoloop the anterior fundus would be approximated to the esophagogastric junction and thus completing the partial anterior fundoplication. Abdominal paracentesis to treat capnoperitoneum would be performed as required based on patient's clinical condition.
  arm group label: Conventional POEM
  arm group type: Active Comparator
  description: Conventional per-oral endoscopic myotomy An anterior POEM would be performed per usual manner described in the literature. The procedure would be performed under general anaesthesia by expert endoscopists with at least 50 case experience of conventional POEM and 5 cases experience of POEM-F. The requirement of POEM experience is based on a recent multicenter study of learning curve by Fujiyoshi Y, et al. The procedure would follow the current recommendations from expert panel in reducing GER, including avoidance of excessive gastric myotomy and preservation of the sling fibers are the gastric cardia. The length of the esophageal and gastric myotomy is standardized at 5cm and 2cm respectively
  intervention type: Procedure
  intervention name: POEM-F
  description: POEM-F would be performed as described in the arms section
  arm group label: Per-oral endoscopic myotomy with fundoplication
  intervention type: Procedure
  intervention name: Conventional POEM
  description: Anterior POEM performed as described in the arms section
  arm group label: Conventional POEM
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Hon Chi Yip, FRCSEd
  role: Principal Investigator
  affiliation: Chinese University of Hong Kong
  last name: Hon Chi Yip, FRCSEd
  phone: 35052627
  email: hcyip@surgery.cuhk.edu.hk
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  country: China
  country: Hong Kong
  country: India
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Chinese University of Hong Kong
  investigator full name: Hon Chi Yip
  investigator title: Assistant Professor
  mesh term: Esophageal Achalasia
  sharing ipd: No