Anti-Reflux Mucosectomy in the Treatment of Refractory Gastro-esophageal Reflux (MARRGO)

Anti-Reflux Mucosectomy (ARMS) in the Treatment of Refractory Gastro-esophageal Reflux (GERD): a Prospective Randomized Comparative Study

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases in Western countries, affecting 8% of the population in its typical and frequent form. For typical GERD without alarming symptoms, treatment combines PPI therapy and lifestyle modifications. Patients with an incomplete response to optimized PPI therapy have so-called refractory GERD. Anti-reflux mucosectomy (ARMS) is a recent technique that achieves endoscopic fundoplication by scar-induced tissue retraction using a mucosal ligation system combined with resection, known as the banded ligation system (ARM-b) [6]. Several studies have shown efficacy of approximately 65-70% on symptom resolution and quality of life improvement, including our pilot study of 21 patients, and without serious adverse events.

The purpose of this study is therefore to prospectively evaluate in a randomized blinded comparison to a sham procedure and conventional medical follow-up, the efficacy of anti-reflux mucosectomy (ARMS) in the treatment of refractory GERD.

The hypothesis is that we can achieve a clinical efficacy rate of 65% in the treatment group versus 35% in the control group.

The primary objective is to demonstrate the superiority in terms of clinical efficacy (self-reported symptom-related GERD rate, GERD-SLR) of RAS compared to the sham procedure combined with optimized medical treatment at 1 year. The primary endpoint will be clinical efficacy, defined as a greater than 50% decrease in the number of GERD-associated symptoms, assessed using the GERD-HRQL score.

Secondary objectives will be:

Assessing clinical efficacy at 6 months. Assess the impact on PPI use Assess changes in procedure-induced abnormal esophageal acid exposure by Ph-metry Assess the impact of this technique on patient quality of life; To document the adverse effects of the technique (AGREE, Clavien Dindo and ASGE score) The duration of follow-up will be 1 year, and based on our hypothesis the number of patients to be included will be 130.

Study Overview

• Status: Recruiting
• Conditions: Gastroesophageal Reflux Disease With Ulceration
• Intervention / Treatment: Procedure: sham; Procedure: endoscopic mucosal resection

• Study Type: Interventional
• Enrollment (Anticipated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jean-Michel Gonzalez, MD; Phone Number: +33 0491368737; Email: jean-michel.gonzalez@ap-hm.fr
• Study Contact Backup: Name: Amandine Rolland-Brun; Phone Number: +33 0491381245; Email: amandine.rolland@ap-hm.fr

Study Locations

• France
  • Marseille, France, 13015
    • Recruiting
    • AP-HM
    • Contact: Jean-Michel Gonzalez, PR; Email: jean-michel.gonzalez@ap-hm.fr

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:

• Patient over 18 years old
• Patient that have read the information form and signed consent
• Patient covered with health insurance
• GERD with typical symptom of pyrosis, or atypical symptoms with clinical symptomatic correlation confirmed by pre-operative Ph-Impedencemetry performed in the last 6 months
• GERD evolving for at least 1 year, and refractory to medical treatment, which is defined by the persistence of daily GERD related symptoms despite PPI at 20mg twice daily associated with local topics and hygiene-dietary measures
• High-resolution manometry (HRM) to eliminate severe motor disorder and research lower esophageal sphincter hypotony performed in the last 6 months
• Eso-gastro-duodenoscopy (EGD) to confirm the absence of severe esophagitis, hiatal hernia, and complicated Barret's esophagus performed in the last 3 months

Exclusion Criteria:

• Grade C peptic esophagitis (Los Angeles classification), persisting despite medical treatment at pre-inclusion gastroscopy (< 6 months)
• Hiatal hernia > 2cm at preoperative gastroscopy
• Barret's Esophagus > C0-M2 with relief abnormalities or confirmed high-grade dysplasia (2 endoscopies within 6 months)
• History of esophageal or gastric surgery
• Severe esophageal motility disorder at HRM such as achalasia or spastic disorder (Chicago classification); minor motility disorders may be included
• No french language comprehension
• Patient under tutelle or curatelle
• Patient already enrolled in interventional research

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: group A: control group	Procedure: sham; The procedure consists of performing endoscopic exploration, no mucosal resection
Experimental: group B: ARMS procedure	Procedure: endoscopic mucosal resection; The procedure consists of performing endoscopic mucosal resection of the 3/4 of the circumference of the esogastric junction using the Duette system (Cook Endoscopy, USA). The procedure will be performed under general anesthesia in an intubated patient, and realized in ambulatory setting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
demonstrate superiority of ARMS	the clinical efficacy defined as the decreasing of self-reported related-symptom GERD assessed using the GERD-HRQL score of more than 50% at one year	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing the clinical efficacy at 6 months	The clinical efficacy, as defined above, at 6 months	6 months
Evaluating the impact on PPIs use after ARMS and sham procedures, respectively;	The rate (and the date) of complete disruption of PPIs at 1 year if so, or, in case of decreasing the mean daily or weekly dose compared to before the intervention	one year
Assessing the changes in abnormal exposure to esophageal acid induced by the procedure	The % time with Ph under 4 on post-operative (3 months) Ph-impedencemetry, compared to pre-operative	3 months
Assessing the changes in abnormal exposure to esophageal acid induced by the procedure	the De Meester score. The interpretation of the score is as follows: DMS <14.72 No GERD; DMS 14.72 - 50 Mild GERD; DMS 51 - 100 Moderate GERD; DMS >100 Severe GERD	3 months
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on Gastrointestinal Quality of Life index (GIQLI) at 2 months These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	2 months
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on Gastrointestinal Quality of Life index (GIQLI) at 4 months These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	4 months
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on Gastrointestinal Quality of Life index (GIQLI) at 6 months. These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	6 months
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on Gastrointestinal Quality of Life index (GIQLI) at 1 year. These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	one year
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on SF12 scores at 2 months. These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	2 months
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on SF12 scores at 4 months. These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	4 months
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on SF12 scores at 6 months. These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	6 months
Evaluating the impact of this technique on patients' quality of life;	The quality of life based on SF12 scores at 1 year. These scores are validated to assess the quality of life specific to digestive diseases. They are free of used and traduced in French. there is no report on a scale	one year
Documenting the adverse events of the technique;	The adverse events rate of ARMS procedure, evaluated per-operatively and until 30 post-operative days, their severity assessed using the AGREE classification, and their management	one year

Collaborators and Investigators

• Sponsor: Assistance Publique Hopitaux De Marseille

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Anticipated): November 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: September 5, 2022
• First Submitted That Met QC Criteria: February 15, 2023
• First Posted (Estimate): February 27, 2023

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: 2022-A00599-34

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