Endoscopic Fundoplication With MUSE System

Recruiting

• Conditions: Gastro-esophageal Reflux; Endoscopic Fundoplication

• Registration Number: NCT03669874
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

This is a spontaneous, prospective, monocentric, observational, cohort study, with the aim of evaluating the effect of ultrasound-guided endoscopic fundoplication using the Medigus Ultrasonic Surgical Endostapler (MUSESystem; MediGus, Ltd. Israel) in patients with esophageal or extra-esophageal gastro-oesophageal reflux disease (GERD)-related symptoms. The end of the study will be at the end of the 6-year follow-up of the last patient enrolled. The study proposes the following objectives:

* Primary objective: to evaluate the efficacy of endoscopic fundoplication with MUSE for the treatment of GERD, through clinical experience, in terms of:

* effect on GERD-Health Related Quality of Life (HRQL) and Reflux Symptom Index (RSI) questionnaire scores

* effect on the use and dosage of proton pump inhibitors (PPI)

* feasibility and safety of the endoluminal fundoplication procedure

* Secondary objective: to characterize the treated patient population (demographic and objective data) and to identify the successful predictors of the procedure.

The study design includes the following phases:

\*Preliminary patient evaluation and verification of inclusion criteria through: Upper GI endoscopy Esophageal high-resolution manometry 24-hours esophageal pH-impedance OFF PPI PPI use GERD-HRQL and RSI questionnaires scores OFF PPI

* 6-month follow-up: Upper GI endoscopy Esophageal high-resolution manometry 24-hours esophageal pH-impedance OFF PPI PPI use GERD-HRQL and RSI questionnaires scores OFF PPI

* 12-months follow-up: Upper GI endoscopy 24-hours esophageal pH-impedance OFF PPI PPI use GERD-HRQL and RSI questionnaires scores OFF PPI

* Yearly clinical follow-up (up to 6 years):

PPI use GERD-HRQL and RSI questionnaires scores OFF PPI

Detailed Description

Not available

Study Timeline

• Study Start: 2015-09-16
• Study First Submitted: 2018-08-30
• Study First Submitted QC: 2018-09-11
• Study First Posted: 2018-09-13
• Status Verified: 2020-12
• Last Update Submitted: 2020-12-10
• Last Update Posted: 2020-12-11
• Primary Completion: 2021-09-16
• Study Completion: 2026-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Chronic (> 6 months) GERD-related esophageal or extra-esophageal symptoms
• Endoscopic or pH-impedance evidence of GERD (esophagitis, Barrett's esophagus, NERD, hypersensitive esophagus)
• Indication to surgical fundoplication
• Patients available for a long-term follow-up

Exclusion Criteria

• Hiatal hernia ≥ 3 cm
• Major esophageal motility disorder
• Esophageal stenosis
• Malignant neoplasia (except minor superficial skin neoplasm)
• Portal hypertension, bleeding disorders so to controindicate surgery, esophageal varices, stenosis or diverticula
• Previous cardiac, thoracic or upper GI surgery
• BMI >40
• Pregnancy or breast feeding

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score	change from baseline RSI at 6 years	RSI is a validate questionnaire to evaluate GERD-related extra- esophageal symptoms. The scale range is (0-45); the higher values represents worse outcomes.
To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption	change from baseline PPI consumption at 6 years	Gastric antisecretive therapy with proton pump inhibitors (PPI) is the gold standard for the treatment of GERD. This therapy is a chronic therapy with possible side effects. The endoscopic procedure under study aims to halved or discontinue the medical therapy
To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in GERD-HRQL (Gastro-esophageal Reflux Disease-Health Related quality of life) questionnaire score	change from baseline GERD-HRQL at 6 years	GERD-HRQL is a validate questionnaire to evaluate GERD-related esophageal symptoms. The scale range is (0-50); the higher values represents worse outcomes.

Secondary Outcome Measures

Name	Time	Method
To identify endoscopic factors predicting positive outcomes: changes in Hill's grade	change from baseline Hill's grade at 12 months	Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The Hill's grade is a parameter describing the continence characteristics of the sphincter neo-valve. The Hill's grade range from I to IV; the higher grades represents worse outcomes (worse valve's continence).
To identify endoscopic factors predicting positive outcomes: changes in esophagitis' grade	change from baseline esophagitis' grade at 12 months	Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The presence of esophagitis and its grade, as defined by the Los Angeles classification, is a parameter of procedure's efficacy. The esophagitis grade range from A to D; the higher grades represents worse outcomes.
To identify endoscopic factors predicting positive outcomes: changes in hiatal hernia size	change from baseline hiatal hernia size at 12 months	Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The size of a hiatal hernia is a parameter describing the continence characteristics of the sphincter neo-valve.
To identify pathophysiological factors predicting positive outcomes: changes in AET (Acid Exposure Time)	change from baseline AET at 12 months	parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in number of weakly acid refluxes	change from baseline number of weakly acid refluxes at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) lenght	change from baseline LES lenght at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.
To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) IRP (Integrated Relaxation Pressure)	change from baseline LES IRP at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.
To identify pathophysiological factors predicting positive outcomes: changes in DeMeester score	change from baseline DeMeester score at 12 months	parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux. DeMeester score is a composite score which examined six variables (number of reflux episodes, number of episodes longer than 5 minutes, longest reflux duration, total percentage of monitoring time with pH below 4, and the percentage of time with pH below 4 in an upright position and supine position). A score of \>14.72 shows a pathological reflux. Higher values represent worse outcomes.
To identify pathophysiological factors predicting positive outcomes: changes in BCT (Bolus Clearance Time)	change from baseline BCT at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify endoscopic factors predicting positive outcomes: changes in Jobe's lenght	change from baseline Jobe's lenght at 12 months	Endoscopic fundoplication with MUSE modifies the anatomy of the esophago-gastric junction to reduce the reflux of gastric contents into the esophagus. The Jobe's lenght is a parameter describing the continence characteristics of the sphincter neo-valve.
To identify pathophysiological factors predicting positive outcomes: changes in MNBI (Mean Nocturnal Baseline Impedance)	change from baseline MNBI at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in longest reflux episode (min)	change from baseline longest reflux episode at 12 months	parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in number of refluxes greater than 5 minutes	change from baseline number of refluxes greater than 5 minutes at 12 months	parameter detected by 24hours esophagel pH-metry. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in number of total refluxes	change from baseline number of total refluxes at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in number of acid refluxes	change from baseline number of acid refluxes at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in DCI (Distal Contractile Integral)	change from baseline DCI at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.
To identify pathophysiological factors predicting positive outcomes: changes in rate of peristaltic waves	change from baseline rate of peristaltic waves at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.
To identify pathophysiological factors predicting positive outcomes: changes in number of not acid refluxes	change from baseline number of not acid refluxes at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in number of proximal refluxes	change from baseline number of proximal refluxes at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in PSPW (Post Swallow reflux-induced Peristaltic Waves)	change from baseline PSPW at 12 months	parameter detected by 24hours esophagel impedance. pH-metric and impedance parameters are indicators of procedure effectiveness as able to quantify the presence of gastro-esophageal reflux.
To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) basal pressure	change from baseline LES basal pressure at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.
To identify pathophysiological factors predicting positive outcomes: changes in rate of weak waves	change from baseline rate of weak waves at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.
To identify pathophysiological factors predicting positive outcomes: changes in rate of fragmented waves	change from baseline rate of fragmented waves at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.
To identify pathophysiological factors predicting positive outcomes: changes in rate of failed waves	change from baseline rate of failed waves at 12 months	parameter detected by High Resolution Esophageal Manometry (HRM). The manometric parameters describe the continence characteristics of the sphincter neo-valve and changes in esophageal motility after the intervention.

Trial Locations

Locations (1)

Pier Alberto Testoni; 🇮🇹 Milan, Italy