Assessment of Different Modified POEM for Achalasia

Study Overview
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Brief Summary
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The aims of this study are 1) to compare the efficacy and safety of conventional myotomy (long myotomy) and modified myotomy (short myotomy) in the treatment of type I/II achalasia patients diagnosed according to Chicago Classification; 2) to compare the efficacy and safety of conventional myotomy (circular myotomy) and modified myotomy (full-thickness myotomy) in the treatment of type I/II achalasia patients; 3) to compare the efficacy and safety of conventional myotomy (non-tailored myotomy) and modified myotomy (tailored myotomy) in the treatment of type III achalasia patients.

Detailed Description
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Peroral endoscopic myotomy (POEM) is a novel clinical technique used to treat achalasia. The conventional POEM myotomy length averages 8 to 10 cm (4-6 cm in the esophagus, 2-4cm in the LES, 2cm in the cardia & 6-8 cm above and 2 cm below the gastroesophageal junction [GEJ]) for typical achalasia (Chicago classification I, II), but there is no guideline or expert consensus with regard to minimal myotomy length recommended in POEM. Based on the facts that achalasia is a primary motor disorder of LES dysfunction, patients with type I/II achalasia may achieve a satisfactory outcome with shorter myotomy in procedure of modified POEM, which only focused on the forced relaxation of the LES. Recently, some retrospective studies have suggested that shorter myotomy is comparable with longer myotomy for treating achalasia with regard to clinical efficacy and has the advantage of shorter procedure time, which needs to be further confirmed by more prospective studies. In terms with the International Peroral Endoscopic Myotomy Survey, a longer myotomy is recommended for patients with type III achalasia. The length of myotomy in type III achalasia can be gauged by high-resolution manometry (HRM). Recent research showed that postoperative Eckardt score was significantly improved in the tailored group (myotomy length informed by HRM) versus non-tailored for type III achalasia, but this study was limited by its retrospective nature. There is still no conclusion on the thickness of muscle bundle dissection recommended during POEM. Selective circular muscle myotomy is designed to avoid gastroesophageal reflux (GER) postoperatively and decrease morbidity during POEM. But one meta-analysis showed that Heller's surgery could keep patients in long-time remission, mainly because of its full-thickness muscle bundle dissection to make sure of persist relaxation of LES. A retrospective study comparing the outcomes of full-thickness and circular muscle myotomy showed no differences in efficacy, GER or adverse events, although the procedural time was shorter in the full thickness myotomy group. Further randomized controlled trials are warranted to assess the efficacy and safety of different modified myotomy approaches in POEM for patients with achalasia.

Official Title
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Comparison Study of Conventional Peroral Endoscopic Myotomy (POEM) and Different Modified Procedures of POEM for Achalasia

Conditions
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Esophageal Achalasia

Intervention / Treatment
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* Procedure: conventional myotomy
* Procedure: short myotomy
* Procedure: full-thickness myotomy
* Procedure: tailored myotomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects diagnosed as achalasia type I, II, or III on the basis of the results of established methods (barium swallow, manometry, esophagogastroduodenoscopy) Candidate for a POEM No contra-indication to general anesthesia Their age is ≥14years and ≤70 years Able to give written consent Exclusion Criteria: Previous myotomy for achalasia: any of previous Heller myotomy, endoscopic myotomy Previous mediastinal surgery Any anatomical esophageal anomaly that in the opinion of the investigator may render the intervention more difficult, such as sigmoid esophagus on the pre-operative barium swallow, esophageal diverticula or hiatal hernia. Any medical condition, which in the judgment of the Investigator and/or designee makes the subject a poor candidate for the investigational procedure Pregnant or lactating female Subjects with coagulopathy

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: conventional myotomy<br>conventional myotomy for achalasia type I, II and III | Procedure: conventional myotomy<br>* Initial mucosal incision. After submucosal injection, a reverse T entry incision is made at approximately 10 cm proximal to the gastroesophageal junction (GEJ). Submucosal tunnel establishment. A submucosal tunnel is created to 2-3 cm distal to the GEJ. Endoscopic myotomy. A selective circular muscle myotomy is carried out in a proximal to distal direction, from 2 cm distal to the mucosal entry down to 2 cm distal to the GEJ. Zippered closure of mucosal entry. The mucosal incision is closed using hemostatic clips.<br>* Other names: non-tailored myotomy;|
| Experimental: short myotomy<br>modified myotomy (short myotomy) for achalasia type I and II | Procedure: short myotomy<br>* Initial mucosal incision. After submucosal injection, a reverse T entry incision is made at approximately 6 cm proximal to the gastroesophageal junction (GEJ). Submucosal tunnel establishment. A submucosal tunnel is created to 2-3 cm distal to the GEJ. Endoscopic myotomy. A selective circular muscle myotomy is carried out in a proximal to distal direction, from 2 cm distal to the mucosal entry down to 2 cm distal to the GEJ. Zippered closure of mucosal entry. The mucosal incision is closed using hemostatic clips.<br>* Other names: modified myotomy;|
| Experimental: full-thickness myotomy<br>modified myotomy (full-thickness myotomy) for achalasia type I and II | Procedure: full-thickness myotomy<br>* Initial mucosal incision. After submucosal injection, a reverse T entry incision is made at approximately 10 cm proximal to the gastroesophageal junction (GEJ). Submucosal tunnel establishment. A submucosal tunnel is created to 2-3 cm distal to the GEJ. Endoscopic myotomy. A selective circular muscle myotomy is carried out in a proximal to distal direction, from 2 cm distal to the mucosal entry down to 4 cm proximal to the GEJ, and a full-thickness muscle myotomy is continually carried out from 4cm proximal to the GEJ down to 2 cm distal to the GEJ. Zippered closure of mucosal entry. The mucosal incision is closed using hemostatic clips.<br>* Other names: modified myotomy;|
| Experimental: tailored myotomy<br>modified myotomy (tailored myotomy) for achalasia type III | Procedure: tailored myotomy<br>* Initial mucosal incision. After submucosal injection, a reverse T entry incision is made at approximately 2 cm proximal to the spastic segment within the esophageal body, which is identified based on information gained from high-resolution manometry (HRM). Submucosal tunnel establishment. A submucosal tunnel is created to 2-3 cm distal to the GEJ. Endoscopic myotomy. A selective circular muscle myotomy is carried out in a proximal to distal direction, from 2 cm distal to the mucosal entry down to 2 cm distal to the GEJ. Zippered closure of mucosal entry. The mucosal incision is closed using hemostatic clips.<br>* Other names: modified myotomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic success of short term | Therapeutic success is defined as a reduction in the Eckardt score to ≤3. The Eckardt score is the sum of the symptom scores for dysphagia, regurgitation, and chest pain (with a score of 0 indicating the absence of symptoms, 1 indicating occasional symptoms, 2 indicating daily symptoms, and 3 indicating symptoms at each meal) and weight loss (with 0 indicating no weight loss, 1 indicating a loss of <5 kg, 2 indicating a loss of 5 to 10 kg, and 3 indicating a loss of >10 kg) (Eckardt, V. Gastroenterology, 1992. 103(6): 1732-8. | 6 months after the procedure | 
| Therapeutic success of long term | Therapeutic success is defined as a reduction in the Eckardt score to ≤3. | 2 years after the procedure | 
| Rate of intra-procedure complications | Complications encountered during the procedure will be noted. (perforation, delayed bleeding, pneumothorax, subcutaneous emphysema, anastomotic leak etc.) | During the endoscopic procedure | 
| Rate of GERD | Gastro-esophageal reflux disease (GERD) is identified by positive results of esophageal pH-impedance/pH-monitoring (DeMeester score), gastro-esophageal reflux symptom assessment (GerdQ questionnaire) or esophagogastroduodenoscopy (reflux esophagitis). | 2 years after the procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Procedure time | The duration of the endoscopic procedures for each patients will be calculated, in minutes, since the mucosal incision until the endoscopic closure of the mucosal entry with the last endoscopic clip. | During the endoscopic procedure | 
| Pressure changes by high-resolution manometry (HRM) | Basal lower esophageal sphincter (LES) pressure and integrated relaxation pressure (IRP) | 2 years after the procedure | 
| Change in barium column height by barium esophagogram | Barium swallow studies will be done to evaluate the oesophageal emptying at 5 minutes | 2 years after the procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peroral endoscopic myotomy, Achalasia