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Endoscopic Versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia

Not Applicable
Completed
Conditions
Achalasia
Interventions
Procedure: Peroral Endoscopic Myotomy (POEM)
Procedure: Laparoscopic Heller Myotomy (LHM)
Registration Number
NCT01601678
Lead Sponsor
Universitätsklinikum Hamburg-Eppendorf
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
240
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Peroral Endoscopic Myotomy POEMPeroral Endoscopic Myotomy (POEM)Patients with Achalasia, designated to receive a myotomy of the lower esophageal sphincter, who have been randomised into the POEM therapy group
Laparoscopic Heller Myotomy LHMLaparoscopic Heller Myotomy (LHM)Patients with Achalasia, designated to receive a myotomy of the lower esophageal sphincter, who have been randomised into the LHM therapy group.
Primary Outcome Measures
NameTimeMethod
Eckhard symptom scores2 years after treatment

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

Secondary Outcome Measures
NameTimeMethod
Eckhard symptom scoresbefore,and 3 and 6 months, 1,3 and 5 years past procedure

Achalasia symptom questionnaire to evaluate individual therapy success, range from 0 (no Achalasia symptoms) to 12 (full symptom range)

Reflux score (clinical DeMeester score)before, and 3 and 6 months, and 1, 2, 3, and 5 years post procedure

clinical DeMeester Reflux questionnaire to evaluate therapeutic side effects, range from 0 (no Reflux symptoms) to 6 (full symptom range).

Adverse EventsBaseline to five years past procedure

complication rate (Adverse Events (AE) and Serious Adverse Events (SAE))

Reflux symptomsbefore, and 3 and 6 months, and 1, 2, 3, and 5 years post procedure

List of side effects due to reflux past POEM as short term and long term outcomes

pH metry3 months and 2 and 5 years after therapy

pH metry data after therapy

Treatment success rates3 and 6 months, and 1, 3, and 5 years post procedure

success rates result from Eckardt Scores

EGD findings3 months and (optional) 2 and 5 years after therapy

EGD findings to evaluate reflux effects after therapy

CRP lab valuesday before procedure to day after procedure

CRP values measured in mg/l (milligrams per litre) pre and post procedure

Leucocyte lab valuesday before procedure to day after procedure

Leucocyte values measured in billions per litre pre and post procedure, number of days of hospitalisation, myotomy length, duration of procedure

Manometry databefore, and 3 months, and 2 and 5 years post procedure

Achalasia subtypes (before treatment) and assessment of lower esophagus sphincter function

Quality of Life indexbefore, and 3 months, and 2 and 5 years post procedure

Life quality assessment (gastrointestinal LQ index by Eypasch, Wood-Dauphinee and Troidl) for individual success Evaluation (GIQLI), Best outcome score is 144.

number of days of hospitalisationthrough inhouse stay after procedure, an average of 2-7 days

inhouse stay after procedure

myotomy lengthday of procedure

myotomy length in cm

Therapy failuresfrom procedure to 5 years after procedure

number of therapy failures

Hb lab valuesday before procedure to day after procedure

Hemoglobin values measured in g/dl (grams per decilitre) pre and post procedure

duration of procedureday of procedure

duration of procedure in minutes

Retreatmentsfrom procedure to 5 years after procedure

number and kinds of retreatments

Trial Locations

Locations (8)

Ersta Hospital and Karolinska University Hospital

🇸🇪

Stockholm, Sweden

University Hospital Leuven

🇧🇪

Leuven, Belgium

University Hospital Prague (IKEM)

🇨🇿

Prague, Czechia

Klinikum Augsburg,Klinik für Innere Medizin III

🇩🇪

Augsburg, Germany

University Hospital Würzburg

🇩🇪

Würzburg, Germany

Universitätsklinikum Eppendorf

🇩🇪

Hamburg, Germany

Istituto Clinico Humanitas

🇮🇹

Rozzano, Italy

Academic Medical Center

🇳🇱

Amsterdam, Netherlands

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