Clinical trial NCT01601678: Endoscopic Versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia
Official title: Endoscopic Versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia: A Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Achalasia
Keywords: Achalasia
Heller Myotomy
Dysphagia
Peroral Endoscopic Myotomy
LHM
POEM
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Karolinska University Hospital
name: University Hospital Prague (IKEM), Prague, Czech Republic
name: Universitaire Ziekenhuizen KU Leuven
name: Istituto Clinico Humanitas
name: Wuerzburg University Hospital
name: University Hospital Augsburg
First posted: 2012-05-18
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Eckhard symptom scores
timeFrame: 2 years after treatment
Secondary outcomes:
measure: Eckhard symptom scores
timeFrame: before,and 3 and 6 months, 1,3 and 5 years past procedure
measure: Treatment success rates
timeFrame: 3 and 6 months, and 1, 3, and 5 years post procedure
measure: Manometry data
timeFrame: before, and 3 months, and 2 and 5 years post procedure
measure: Reflux score (clinical DeMeester score)
timeFrame: before, and 3 and 6 months, and 1, 2, 3, and 5 years post procedure
measure: Reflux symptoms
timeFrame: before, and 3 and 6 months, and 1, 2, 3, and 5 years post procedure
measure: pH metry
timeFrame: 3 months and 2 and 5 years after therapy
measure: Adverse Events
timeFrame: Baseline to five years past procedure
measure: Quality of Life index
timeFrame: before, and 3 months, and 2 and 5 years post procedure
measure: EGD findings
timeFrame: 3 months and (optional) 2 and 5 years after therapy
measure: CRP lab values
timeFrame: day before procedure to day after procedure
measure: Hb lab values
timeFrame: day before procedure to day after procedure
measure: Leucocyte lab values
timeFrame: day before procedure to day after procedure
measure: number of days of hospitalisation
timeFrame: through inhouse stay after procedure, an average of 2-7 days
measure: myotomy length
timeFrame: day of procedure
measure: duration of procedure
timeFrame: day of procedure
measure: Therapy failures
timeFrame: from procedure to 5 years after procedure
measure: Retreatments
timeFrame: from procedure to 5 years after procedure
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven
city: Prague
country: Czechia
facility: University Hospital Prague (IKEM)
city: Augsburg
country: Germany
facility: Klinikum Augsburg,Klinik für Innere Medizin III
city: Hamburg
country: Germany
facility: Universitätsklinikum Eppendorf
city: Würzburg
country: Germany
facility: University Hospital Würzburg
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Stockholm
country: Sweden
facility: Ersta Hospital and Karolinska University Hospital
Study officials:
affiliation: Interdisciplinary Endoscopy Department and Clinic, University Hospital Hamburg-Eppendorf, Germany
name: Thomas Roesch, Prof.
role: STUDY_DIRECTOR
affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam; Netherlands
name: Paul Fockens, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department of Surgery, Karolinska University Hospital, Stockholm, Sweden
name: Bengt Håkanson, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Guy Boeckxstaens, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Wuerzburg University Hospital
name: C.T. Germer, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Clinico Humanitas, Rozzano, Italy
name: Riccardo Repici, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Istituto Clinico Humanitas, Rozzano, Italy
name: Uberto Fumagalli, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital Prague, Prague, Czech Republic
name: Julius Spicak, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Department for Internal Medicine III, Klinikum Augsburg, Germany
name: Helmut Messmann, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
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