Anti-Reflux Mucosectomy in the Treatment of Refractory Gastro-esophageal Reflux

Study Overview
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Brief Summary
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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.

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

Conditions
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Gastroesophageal Reflux Disease With Ulceration

Intervention / Treatment
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* Procedure: endoscopic mucosal resection
* Procedure: sham


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: group A: control group<br> | Procedure: sham<br>* The procedure consists of performing endoscopic exploration, no mucosal resection<br>|
| Experimental: group B: ARMS procedure<br> | Procedure: endoscopic mucosal resection<br>* 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.<br>|

What is the study measuring?
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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 |