POEM: Long vs Short Myotomy for Achalasia. RCT

Peroral Endoscopic Myotomy (POEM) for the Treatment of Esophageal Achalasia: Long vs Short Myotomy. Prospective Randomized Controlled Study

Per-Oral Endoscopic Myotomy (POEM) is increasingly used for the treatment of achalasia. In published series, a 12cm-POEM is usually performed. Surgical myotomy is typically shorter (8cm). The clinical efficacy of both procedure is comparable.

This study intends to investigate if clinical outcomes of POEM depends on the length of esophageal myotomy, in patients with classic-type achalasia (type I and type II according to Chicago Classification)

Study Overview

• Status: Unknown
• Conditions: Achalasia
• Intervention / Treatment: Procedure: Peroral Endoscopic Myotomy (POEM)

Detailed Description

Peroral Endoscopic Myotomy myotomy (POEM) has been recently introduced for treatment of achalasia, based on technical developments from NOTES (natural orifice translumenal surgery). The technique includes the incision of the mucosa in the esophageal body, the submucosal dissection of the distal esophagus and the creation of a submucosal tunnel in the distal esophagus and proximal gastric body, and the esophageal myotomy. The procedure is performed transorally, using a flexible endoscope.

In published series, a 12cm-POEM is usually performed. Surgical myotomy is typically shorter, being protracted for about 8cm. The clinical efficacy of POEM and surgical myotomy is more likely to be similar according to the most recent published series.

In this randomized controlled trial (non-inferiority trial) we evaluate the outcomes of POEM according to the length of the esophageal myotomy.

Patients with type I and II achalasia will be randomly assigned to one of the two groups, long--myotomy (LM) and short--myotomy (SM).

Patients in the LM-group will receive a 12cm-long POEM (including 3cm on the stomach); in the SM-group patients will undergo a POEM extended for 7 cm (including 3cm on the stomach).

During follow-up, High Resolution Manometry (HRM), Esophageal pH-monitoring study and Esophagogastroduodenoscopy (EGD) will be regularly performed and symptoms assessed with the use of the Eckardt score (ECKs).

The main hypothesis is that the results of a SM are not inferior to the results of a LM. Calculated sample size is 200 patients

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • RM
    • Roma, RM, Italy, 00168
      • Recruiting
      • Fondazione Policlinico Universitario Agostino Gemelli
      • Contact: Carolina Gualtieri; Phone Number: 00390630156580; Email: carolina.gualtieri@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of achalasia (type I and II)
2. Age > 18
3. Signed informed consent
4. Patient accepts to undergo scheduled follow-up after POEM
5. Eckardt score > 3
6. ASA I-II-III

Exclusion Criteria:

1. Prior surgical treatment of achalasia (previous endoscopic balloon dilation or botox injection ARE NOT exclusion criteria)
2. Pregnancy or nursing
3. Current alcohol or drug addiction.
4. Mentally retarded or emotionally unstable, or exhibits psychological characteristics which, in the opinion of the investigator make the subject a poor candidate for this study.
5. Severe congenital or acquired coagulopathy or INR > 1.6
6. Participating in another ongoing clinical trial in which concomitant diagnosis or therapeutic intervention would adversely affect the integrity of the clinical trial.
7. Hepatic cirrhosis w/ or w/o portal hypertension w/ or w/o esophageal varices
8. Eosinophilic esophagitis or Barrett Esophagus
9. Esophageal Strictures

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Short POEM; Patients in the Short POEM-group will undergo a Peroral Endoscopic Myotomy (POEM) extended for a total of 7 cm (including 4 cm above the esophago-gastric junction and 3cm on the stomach).	Procedure: Peroral Endoscopic Myotomy (POEM); Peroral endoscopic myotomy (POEM) is a minimally invasive intervention for the treatment of esophageal achalasia. POEM includes different steps: Lifting of the esophageal mucosa, with the injection of saline solution, and mucosal incision on the esophageal body (approximately 12 or 7 cm above the esophagogastric junction, for about 1-2cm); Advance of the endoscope into the submucosa, repeated submucosal injection and dissection of a submucosal tunnel into the distal esophagus up to 3 cm into the gastric wall.; Myotomy of the distal esophagus, cardia and gastric wall, starting 3 cm below the mucosal incision; After the completion of myotomy, and check for mucosal integrity, the mucosal incision is closed using endoscopic clips
Active Comparator: Long POEM; Patients in the Long POEM-group will receive a 12cm-long Peroral Endoscopic Myotomy (POEM), including 9 cm on the esophagus and 3cm on the gastric wall	Procedure: Peroral Endoscopic Myotomy (POEM); Peroral endoscopic myotomy (POEM) is a minimally invasive intervention for the treatment of esophageal achalasia. POEM includes different steps: Lifting of the esophageal mucosa, with the injection of saline solution, and mucosal incision on the esophageal body (approximately 12 or 7 cm above the esophagogastric junction, for about 1-2cm); Advance of the endoscope into the submucosa, repeated submucosal injection and dissection of a submucosal tunnel into the distal esophagus up to 3 cm into the gastric wall.; Myotomy of the distal esophagus, cardia and gastric wall, starting 3 cm below the mucosal incision; After the completion of myotomy, and check for mucosal integrity, the mucosal incision is closed using endoscopic clips

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Non-inferiority of a Short-POEM compared to a Long-POEM	Treatment success, defined as an Eckard score ≤ 3. The Eckardt score is a clinical score for evaluating the severity of achalasia-related symptoms. Eckardt score varies between 0 and 12. Questions are asked about the frequency of dysphagia, regurgitation and retrosternal pressure sensation. Depending on whether any of these symptom occurrs, never, occasionally, daily or with each meal, a symptom score between 0 and 3 is applied. In addition a symptom score of 0-3 is assigned to the degree of weight loss (0 - No weight loss; 1 - weight loss < 5Kg, 2 - weight loss between 5 and 10Kg, 3- weight loss > 10Kg). Each symptom score (dysphagia, regurgitation, retrosternal pressure, and wieight loss) is summed to the other. Thus, a completely asymptomatic patient has a score of 0 and the most severely affected patient had a maximum score of 12.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Basal Lower Esophageal Sphincter (LES) pressure	Basal LES pressure on esophageal manometry after Short-POEM compared to Long-POEM	Before POEM, 6 months and 2 years after the procedure
4-second Integrated Relaxation Pressure (4sIRP)	4sIRP on esophageal manometry after Short-POEM compared to Long-POEM	Before POEM, 6 months and 2 years after the procedure
Side effects and complications	Incidence of side effect and complications after Short-POEM compared to Long-POEM	Baseline to 2 years
Gastro-Esophageal Reflux (GER) symptom assessment	GerdQ questionnaire will be used to evaluate and compare Gastoesophageal reflux symptoms in the two groups. GerdQ is a 6-item, validated, easy to use questionnaire. The GerdQ questionnaire asks patients to score the number of days with symptoms and use of over-the-counter (OTC) medications during the previous 7 days. It uses a four graded Likert scale (0-3) to score the frequency of four positive predictors of GERD (heartburn, regurgitation, sleep disturbance due to reflux symptoms or use of over-the-counter (OTC) medications for reflux symptoms) and a reversed Likert scale (3-0) for two negative predictors of GERD (epigastric pain and nausea) giving a total GerdQ score range of 0-18. The sleep disturbance and use of OTC medication are also used for assessment of the impact of GERD, giving a separate 'impact score' ranging from 0 to 6	baseline, 6 months and 2 years after POEM
Esophageal pH-monitoring study	patients will undergo esophageal pH-monitoring study during the follow-up. DeMeester score will be used for the diagnosis of GERD. DeMeester score is a composite score based on 6 parameters (scored in comparison to mean values in normal subjects for each category below): Supine reflux, Upright reflux, Total reflux, Number of episodes, Number of episodes longer than 5 min, Longest episode. A score of >14.72 shows significant reflux. Prevalence of GERD will be compared in the two study groups	6 months after POEM
Operating 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. The average duration of the procedure in the Short-POEM group will be compared wth the dureation of the procedures in the Long-POEM-groups	During the endoscopic procedure
Quality of life	Improvement of quality of life after Short-POEM compared to Long-POEM, assessed by using the SF-36 questionnaires' scores The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability i.e., a score of zero is equivalent to maximum disability and a score of 100 is equivalent to no disability. The eight sections are: vitality, physical functioning, bodily pain, general health perceptions, physical role functioning, emotional role functioning, social role functioning, mental health	baseline, 6 months and 2 years

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2014
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2022

Study Registration Dates

• First Submitted: November 7, 2017
• First Submitted That Met QC Criteria: February 23, 2018
• First Posted (Actual): March 1, 2018

Study Record Updates

• Last Update Posted (Actual): March 1, 2018
• Last Update Submitted That Met QC Criteria: February 23, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: Endoscopy; POEM; Peroral Endoscopic Myotomy; Submucosal endoscopy
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Esophageal Achalasia
• Other Study ID Numbers: POEMLvS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No