Endoscopic Versus Laparoscopic Myotomy for Treatment of Idiopathic Achalasia

Achalasia Clinical Trial

— POEMrct  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01601678
• Other study ID #: POEM vs. LHM
• Secondary ID: PV 4133
• Status: Completed
• Phase: N/A
• Start date: December 2012
• Est. completion date: May 30, 2023

Study information

• Verified date: June 2023
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: May 30, 2023
• Est. primary completion date: May 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Achalasia
• Esophageal Achalasia

Intervention

Procedure:
• Peroral Endoscopic Myotomy (POEM)
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.
• Laparoscopic Heller Myotomy (LHM)
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.

Locations

Country	Name	City	State
Belgium	University Hospital Leuven	Leuven
Czechia	University Hospital Prague (IKEM)	Prague
Germany	Klinikum Augsburg,Klinik für Innere Medizin III	Augsburg
Germany	Universitätsklinikum Eppendorf	Hamburg
Germany	University Hospital Würzburg	Würzburg
Italy	Istituto Clinico Humanitas	Rozzano
Netherlands	Academic Medical Center	Amsterdam
Sweden	Ersta Hospital and Karolinska University Hospital	Stockholm

Sponsors (8)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Istituto Clinico Humanitas, Karolinska University Hospital, Universitaire Ziekenhuizen KU Leuven, University Hospital Augsburg, University Hospital Prague (IKEM), Prague, Czech Republic, Wuerzburg University Hospital

Countries where clinical trial is conducted

Belgium,  Czechia,  Germany,  Italy,  Netherlands,  Sweden, 

References & Publications (12)

Boeckxstaens GE, Annese V, des Varannes SB, Chaussade S, Costantini M, Cuttitta A, Elizalde JI, Fumagalli U, Gaudric M, Rohof WO, Smout AJ, Tack J, Zwinderman AH, Zaninotto G, Busch OR; European Achalasia Trial Investigators. Pneumatic dilation versus laparoscopic Heller's myotomy for idiopathic achalasia. N Engl J Med. 2011 May 12;364(19):1807-16. doi: 10.1056/NEJMoa1010502. — View Citation

Campos GM, Vittinghoff E, Rabl C, Takata M, Gadenstatter M, Lin F, Ciovica R. Endoscopic and surgical treatments for achalasia: a systematic review and meta-analysis. Ann Surg. 2009 Jan;249(1):45-57. doi: 10.1097/SLA.0b013e31818e43ab. — View Citation

Inoue H, Minami H, Kobayashi Y, Sato Y, Kaga M, Suzuki M, Satodate H, Odaka N, Itoh H, Kudo S. Peroral endoscopic myotomy (POEM) for esophageal achalasia. Endoscopy. 2010 Apr;42(4):265-71. doi: 10.1055/s-0029-1244080. Epub 2010 Mar 30. — View Citation

Ortiz A, de Haro LF, Parrilla P, Lage A, Perez D, Munitiz V, Ruiz D, Molina J. Very long-term objective evaluation of heller myotomy plus posterior partial fundoplication in patients with achalasia of the cardia. Ann Surg. 2008 Feb;247(2):258-64. doi: 10.1097/SLA.0b013e318159d7dd. — View Citation

Pasricha PJ, Hawari R, Ahmed I, Chen J, Cotton PB, Hawes RH, Kalloo AN, Kantsevoy SV, Gostout CJ. Submucosal endoscopic esophageal myotomy: a novel experimental approach for the treatment of achalasia. Endoscopy. 2007 Sep;39(9):761-4. doi: 10.1055/s-2007-966764. — View Citation

Perretta S, Dallemagne B, Allemann P, Marescaux J. Multimedia manuscript. Heller myotomy and intraluminal fundoplication: a NOTES technique. Surg Endosc. 2010 Nov;24(11):2903. doi: 10.1007/s00464-010-1073-3. Epub 2010 Apr 29. Erratum In: Surg Endosc.2010 Nov;24(11):2904. Alleman, Pierre [corrected to Allemann, Pierre]. — View Citation

Rebecchi F, Giaccone C, Farinella E, Campaci R, Morino M. Randomized controlled trial of laparoscopic Heller myotomy plus Dor fundoplication versus Nissen fundoplication for achalasia: long-term results. Ann Surg. 2008 Dec;248(6):1023-30. doi: 10.1097/SLA.0b013e318190a776. — View Citation

Smith CD, Stival A, Howell DL, Swafford V. Endoscopic therapy for achalasia before Heller myotomy results in worse outcomes than heller myotomy alone. Ann Surg. 2006 May;243(5):579-84; discussion 584-6. doi: 10.1097/01.sla.0000217524.75529.2d. — View Citation

Swanstrom LL, Rieder E, Dunst CM. A stepwise approach and early clinical experience in peroral endoscopic myotomy for the treatment of achalasia and esophageal motility disorders. J Am Coll Surg. 2011 Dec;213(6):751-6. doi: 10.1016/j.jamcollsurg.2011.09.001. Epub 2011 Oct 13. — View Citation

von Rahden BH, Germer CT. [Laparoscopic myotomy for achalasia is clearly superior to the endoscopic treatment]. Chirurg. 2010 Jan;81(1):69-70. doi: 10.1007/s00104-009-1840-7. No abstract available. German. — View Citation

von Renteln D, Inoue H, Minami H, Werner YB, Pace A, Kersten JF, Much CC, Schachschal G, Mann O, Keller J, Fuchs KH, Rosch T. Peroral endoscopic myotomy for the treatment of achalasia: a prospective single center study. Am J Gastroenterol. 2012 Mar;107(3):411-7. doi: 10.1038/ajg.2011.388. Epub 2011 Nov 8. — View Citation

ZHOU PH, CAI MY, YAO LQ, ZHONG YS, REN Z, XU MD, CHEN WF, QIN XY. [Peroral endoscopic myotomy for esophageal achalasia: report of 42 cases]. Zhonghua Wei Chang Wai Ke Za Zhi. 2011 Sep;14(9):705-8. Chinese. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Treatment success rates	success rates result from Eckardt Scores	3 and 6 months, and 1, 3, and 5 years post procedure
Secondary	Manometry data	Achalasia subtypes (before treatment) and assessment of lower esophagus sphincter function	before, and 3 months, and 2 and 5 years post procedure
Secondary	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
Secondary	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
Secondary	pH metry	pH metry data after therapy	3 months and 2 and 5 years after therapy
Secondary	Adverse Events	complication rate (Adverse Events (AE) and Serious Adverse Events (SAE))	Baseline to five years past procedure
Secondary	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
Secondary	EGD findings	EGD findings to evaluate reflux effects after therapy	3 months and (optional) 2 and 5 years after therapy
Secondary	CRP lab values	CRP values measured in mg/l (milligrams per litre) pre and post procedure	day before procedure to day after procedure
Secondary	Hb lab values	Hemoglobin values measured in g/dl (grams per decilitre) pre and post procedure	day before procedure to day after procedure
Secondary	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
Secondary	number of days of hospitalisation	inhouse stay after procedure	through inhouse stay after procedure, an average of 2-7 days
Secondary	myotomy length	myotomy length in cm	day of procedure
Secondary	duration of procedure	duration of procedure in minutes	day of procedure
Secondary	Therapy failures	number of therapy failures	from procedure to 5 years after procedure
Secondary	Retreatments	number and kinds of retreatments	from procedure to 5 years after procedure