Endoscopic Versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia

Study Overview
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Brief Summary
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Achalasia is a rare neurodegenerative esophageal motility disorder characterized by incomplete lower esophageal sphincter (LES) relaxation, increased LES tone, and aperistalsis of the esophagus leading to dysphagia, regurgitation, and chest pain. therapies for achalasia consist of endoscopic balloon dilatation (EBD) and botulinum toxin injection (EBTI), or surgical Treatment via i Heller Myotomy; surgery is nowadays mostly performed via the laparoscopic approach. Surgical therapy demonstrated superior treatment efficacy compared to EBD and EBTI. Recently, an endoscopic means to perform myotomy via a submucosal tunnel has been developed, namely PerOral Endoscopic Myotomy (POEM). Uncontrolled studies have indicated a symptomatic success rate of >90% for POEM in short term follow-ups.The aim of this study is to compare short and long-term feasibility, safety and efficacy of endoscopic (POEM) with laparoscopic myotomy (Heller myotomy) in the treatment of achalasia.

Detailed Description
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Achalasia is considered a primary esophageal motility disorder which is defined as an insufficient relaxation of the lower esophageal sphincter. Incomplete lower esophageal sphincter (LES) relaxation, increased LES tone, and aperistalsis of the esophagus are characteristics of achalasia. Incidence peaks between ages 20 to 40. The most commonly reported symptoms are dysphagia (both for solids and liquids), regurgitation, and chest pain. The diagnosis is established with esophageal manometry and barium swallow radiographic studies and also with endoscopy being performed to exclude neoplastic or inflammatory diseases. Endoscopic therapies consist of either balloon dilatation (EBD) or Botulinum toxin injection (EBTI). The surgical treatment for achalasia is Heller Myotomy, nowadays almost exclusively performed laparoscopically.Superior to EBD and EBTI, surgical myotomy has shown sustained therapeutic efficacy in approximately 90% of patients which may be especially relevant for young patients with achalasia. Recently an endoscopic technique to create myotomy via a submucosal tunnel has been developed, named PerOral Endoscopic Myotomy (POEM). The technique was first reported by Pasricha et al. in a porcine study, and Inoue et al. later reported the first clinical results in achalasia patients which showed significantly reduced dysphagia symptom scores and decreased resting lower esophageal sphincter (LES) pressures in 17 patients with a mean follow-up of 5 months . No serious complications related to POEM were encountered in this initial single-center trial. Several smaller pilot studies from Asia, Europe and USA have replicated the promising results regarding feasibility, safety and short-term efficacy,leading us to hope for a similar success rate along with reduced patient discomfort At present, POEM has the potential to be the first scarless flexible endosurgical intervention to become an established clinical treatment.The technique uses a submucosal esophageal tunnel through which a distal esophageal myotomy down to the proximal stomach is performed. For POEM to be integrated into clinical routine, comparative data regarding safety and efficacy are necessary.Our study group intends to compare safety and long-term efficacy of POEM to laparoscopic Heller myotomy, the current gold-Standard, in a non-inferiority design. Patients with symptomatic achalasia and medical indication for interventional therapy will be randomized to either POEM therapy or standard laparoscopic Heller myotomy (with anti-reflux procedure)(LHM). They will be followed up closely in a defined time pattern evolving individual life quality and achalasia scores as well as clinical scores and diagnostics over a period of 5 years. Due to considerations concerning the comparability to other achalsia Trials (Boeckxstaens,NEJM 2011), in November 2012 primary outcome has been changed to Eckardt Score instead of lower sphicter pressure. Amendment was done before patient inclusion started. Sample size was not affected by amendment.

Official Title
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Endoscopic Versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia: A Randomized, Controlled Trial

Conditions
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Achalasia

Intervention / Treatment
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* Procedure: Peroral Endoscopic Myotomy (POEM)
* Procedure: Laparoscopic Heller Myotomy (LHM)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with symptomatic achalasia with an Eckardt score of > 3 and pre-op barium swallow, manometry and esophagogastroduodenoscopy consistent with the diagnosis Persons of age > 18 years with medical indication for surgical myotomy or EBD Signed written Informed Consent Exclusion Criteria: Patients with previous surgery of the stomach or esophagus Patients with known coagulopathy Previous surgical achalasia treatment Patients with liver cirrhosis and/or esophageal varices Active esophagitis Eosinophilic esophagitis Barrett's esophagus Pregnancy Stricture of the esophagus Malignant or premalignant esophageal lesion Severe Candida esophagitis Hiatal hernia > 1cm Extensive tortuous dilatation (>7cm luminal diameter, S shape) of the esophagus Advanced malignant tumor with prognosis < 2 years

Ages Eligible for Study
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Minimum Age: 18 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: Peroral Endoscopic Myotomy POEM<br>Patients with Achalasia, designated to receive a myotomy of the lower esophageal sphincter, who have been randomised into the POEM therapy group | Procedure: Peroral Endoscopic Myotomy (POEM)<br>* After lavage, measure gastro-esophageal junction (GEJ) in cm from mouth piece. Determine entry point 12-14cm above GEJ at the lesser curvature site, inject 10ml coloured saline, create entry point. Advance endoscope into the submucosa, dissect the submucosal tunnel up to 2-3cm into the cardia. Dissect the submucosa close to the muscularis and check endoluminally for the direction of the lesser curvature, sufficient extension onto the cardia and mucosal integrity. After tunnel completion flush with gentamycin and saline. Start myotomy from proximally to distally starting 4-5cm below the mucosal entry site; the inner circular muscle layer should be fully dissected especially at the cardia for good symptomatic results. It is vital that the mucosa of the tubular esophagus remains intact. Extend myotomy at least 2cm onto the cardia. After completion check for mucosal integrity and opening of the distal esophageal sphincter. Close the entry point with clips from distal to proximal.<br>|
| Active Comparator: Laparoscopic Heller Myotomy LHM<br>Patients with Achalasia, designated to receive a myotomy of the lower esophageal sphincter, who have been randomised into the LHM therapy group. | Procedure: Laparoscopic Heller Myotomy (LHM)<br>* Use five trocar technique with patient in the French position as for laparoscopic anti-reflux procedures. Establish 12-15 mm Hg pneumoperitoneum. Use left paramedian trocar for camera, two lateral trocars for elevating liver and retraction of stomach and two trocars for dissection and suturing. Use of robotic surgery devices is allowed. Divide phrenoesophageal ligament starting on the right and mobilize distal esophagus on the lateral and anterior side. Identify and spare anterior vagal nerve. Perform myotomy by dividing both muscle-layers extending at least 6 cm above gastroesophageal junction and at least 2-3 cm inferiorly over stomach. Perform extent downwards after dividing epiphrenic fat pad overlying cardia. Measure myotomy length. Peroperative endoscopy check is advisable. Perform anterior fundoplication according to Dor. Only if necessary mobilize fundus of the stomach by dividing short gastric vessels. Suture fundus to both cut edges of myotomy, using non-resorbable material.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eckhard symptom scores | Achalasia symptom questionnaire to evaluate individual therapy success, range from 0 (no Achalasia symptoms) to 12 (full symptom range), treatment success is defined as an Eckardt Score ≤ 3 | 2 years after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eckhard symptom scores | Achalasia symptom questionnaire to evaluate individual therapy success, range from 0 (no Achalasia symptoms) to 12 (full symptom range) | before,and 3 and 6 months, 1,3 and 5 years past procedure | 
| Treatment success rates | success rates result from Eckardt Scores | 3 and 6 months, and 1, 3, and 5 years post procedure | 
| Manometry data | Achalasia subtypes (before treatment) and assessment of lower esophagus sphincter function | before, and 3 months, and 2 and 5 years post procedure | 
| Reflux score (clinical DeMeester score) | clinical DeMeester Reflux questionnaire to evaluate therapeutic side effects, range from 0 (no Reflux symptoms) to 6 (full symptom range). | before, and 3 and 6 months, and 1, 2, 3, and 5 years post procedure | 
| Reflux symptoms | List of side effects due to reflux past POEM as short term and long term outcomes | before, and 3 and 6 months, and 1, 2, 3, and 5 years post procedure | 
| pH metry | pH metry data after therapy | 3 months and 2 and 5 years after therapy | 
| Adverse Events | complication rate (Adverse Events (AE) and Serious Adverse Events (SAE)) | Baseline to five years past procedure | 
| Quality of Life index | Life quality assessment (gastrointestinal LQ index by Eypasch, Wood-Dauphinee and Troidl) for individual success Evaluation (GIQLI), Best outcome score is 144. | before, and 3 months, and 2 and 5 years post procedure | 
| EGD findings | EGD findings to evaluate reflux effects after therapy | 3 months and (optional) 2 and 5 years after therapy | 
| CRP lab values | CRP values measured in mg/l (milligrams per litre) pre and post procedure | day before procedure to day after procedure | 
| Hb lab values | Hemoglobin values measured in g/dl (grams per decilitre) pre and post procedure | day before procedure to day after procedure | 
| Leucocyte lab values | Leucocyte values measured in billions per litre pre and post procedure, number of days of hospitalisation, myotomy length, duration of procedure | day before procedure to day after procedure | 
| number of days of hospitalisation | inhouse stay after procedure | through inhouse stay after procedure, an average of 2-7 days | 
| myotomy length | myotomy length in cm | day of procedure | 
| duration of procedure | duration of procedure in minutes | day of procedure | 
| Therapy failures | number of therapy failures | from procedure to 5 years after procedure | 
| Retreatments | number and kinds of retreatments | from procedure to 5 years after procedure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LHM, Achalasia, Heller Myotomy, Dysphagia, Peroral Endoscopic Myotomy, POEM