Clinical trial NCT03669874: Endoscopic Fundoplication With MUSE System
Official title: Clinical Application of MUSE System for Ultrasound-guided Endoscopic Fundoplication for Gastro-esophageal Reflux Disease Patients
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gastro-esophageal Reflux
Endoscopic Fundoplication
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2018-09-13
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients are selected from tertiary care center

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


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: change from baseline GERD-HRQL at 6 months
measure: 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
timeFrame: change from baseline GERD-HRQL at 12 months
measure: 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
timeFrame: change from baseline GERD-HRQL at 24 months
measure: 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
timeFrame: change from baseline GERD-HRQL at 3 years
measure: 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
timeFrame: change from baseline GERD-HRQL at 4 years
measure: 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
timeFrame: change from baseline GERD-HRQL at 5 years
measure: 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
timeFrame: change from baseline GERD-HRQL at 6 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score
timeFrame: change from baseline RSI at 6 months
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score
timeFrame: change from baseline RSI at 12 months
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score
timeFrame: change from baseline RSI at 24 months
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score
timeFrame: change from baseline RSI at 3 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score
timeFrame: change from baseline RSI at 4 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score
timeFrame: change from baseline RSI at 5 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by change in RSI (Reflux Symptom Index) questionnaire score
timeFrame: change from baseline RSI at 6 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption
timeFrame: change from baseline PPI consumption at 6 months
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption
timeFrame: change from baseline PPI consumption at 12 months
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption
timeFrame: change from baseline PPI consumption at 24 months
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption
timeFrame: change from baseline PPI consumption at 3 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption
timeFrame: change from baseline PPI consumption at 4 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption
timeFrame: change from baseline PPI consumption at 5 years
measure: To evaluate clinical efficacy of endoscopic fundoplication with MUSE as assessed by changes in proton pump inhibitors (PPI) consumption
timeFrame: change from baseline PPI consumption at 6 years
Secondary outcomes:
measure: To identify endoscopic factors predicting positive outcomes: changes in hiatal hernia size
timeFrame: change from baseline hiatal hernia size at 6 months
measure: To identify endoscopic factors predicting positive outcomes: changes in hiatal hernia size
timeFrame: change from baseline hiatal hernia size at 12 months
measure: To identify endoscopic factors predicting positive outcomes: changes in Hill's grade
timeFrame: change from baseline Hill's grade at 6 months
measure: To identify endoscopic factors predicting positive outcomes: changes in Hill's grade
timeFrame: change from baseline Hill's grade at 12 months
measure: To identify endoscopic factors predicting positive outcomes: changes in Jobe's lenght
timeFrame: change from baseline Jobe's lenght at 6 months
measure: To identify endoscopic factors predicting positive outcomes: changes in Jobe's lenght
timeFrame: change from baseline Jobe's lenght at 12 months
measure: To identify endoscopic factors predicting positive outcomes: changes in esophagitis' grade
timeFrame: change from baseline esophagitis' grade at 6 months
measure: To identify endoscopic factors predicting positive outcomes: changes in esophagitis' grade
timeFrame: change from baseline esophagitis' grade at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in DeMeester score
timeFrame: change from baseline DeMeester score at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in DeMeester score
timeFrame: change from baseline DeMeester score at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in AET (Acid Exposure Time)
timeFrame: change from baseline AET at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in AET (Acid Exposure Time)
timeFrame: change from baseline AET at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in longest reflux episode (min)
timeFrame: change from baseline longest reflux episode at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in longest reflux episode (min)
timeFrame: change from baseline longest reflux episode at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of refluxes greater than 5 minutes
timeFrame: change from baseline number of refluxes greater than 5 minutes at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of refluxes greater than 5 minutes
timeFrame: change from baseline number of refluxes greater than 5 minutes at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of total refluxes
timeFrame: change from baseline number of total refluxes at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of total refluxes
timeFrame: change from baseline number of total refluxes at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of acid refluxes
timeFrame: change from baseline number of acid refluxes at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of acid refluxes
timeFrame: change from baseline number of acid refluxes at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of weakly acid refluxes
timeFrame: change from baseline number of weakly acid refluxes at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of weakly acid refluxes
timeFrame: change from baseline number of weakly acid refluxes at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of not acid refluxes
timeFrame: change from baseline number of not acid refluxes at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of not acid refluxes
timeFrame: change from baseline number of not acid refluxes at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of proximal refluxes
timeFrame: change from baseline number of proximal refluxes at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in number of proximal refluxes
timeFrame: change from baseline number of proximal refluxes at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in MNBI (Mean Nocturnal Baseline Impedance)
timeFrame: change from baseline MNBI at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in MNBI (Mean Nocturnal Baseline Impedance)
timeFrame: change from baseline MNBI at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in PSPW (Post Swallow reflux-induced Peristaltic Waves)
timeFrame: change from baseline PSPW at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in PSPW (Post Swallow reflux-induced Peristaltic Waves)
timeFrame: change from baseline PSPW at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in BCT (Bolus Clearance Time)
timeFrame: change from baseline BCT at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in BCT (Bolus Clearance Time)
timeFrame: change from baseline BCT at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) basal pressure
timeFrame: change from baseline LES basal pressure at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) basal pressure
timeFrame: change from baseline LES basal pressure at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) lenght
timeFrame: change from baseline LES lenght at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) lenght
timeFrame: change from baseline LES lenght at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) IRP (Integrated Relaxation Pressure)
timeFrame: change from baseline LES IRP at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in LES (Lower Esophageal Sphincter) IRP (Integrated Relaxation Pressure)
timeFrame: change from baseline LES IRP at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in DCI (Distal Contractile Integral)
timeFrame: change from baseline DCI at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in DCI (Distal Contractile Integral)
timeFrame: change from baseline DCI at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of peristaltic waves
timeFrame: change from baseline rate of peristaltic waves at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of peristaltic waves
timeFrame: change from baseline rate of peristaltic waves at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of weak waves
timeFrame: change from baseline rate of weak waves at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of weak waves
timeFrame: change from baseline rate of weak waves at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of fragmented waves
timeFrame: change from baseline rate of fragmented waves at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of fragmented waves
timeFrame: change from baseline rate of fragmented waves at 12 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of failed waves
timeFrame: change from baseline rate of failed waves at 6 months
measure: To identify pathophysiological factors predicting positive outcomes: changes in rate of failed waves
timeFrame: change from baseline rate of failed waves at 12 months
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Pier Alberto Testoni
Study officials:
affiliation: San Raffaele Scientific Institute
name: Pier Alberto Testoni, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Testoni SGG, Cilona MB, Mazzoleni G, Fanti L, Ribichini E, Cavestro GM, Esposito D, Viale E, Notaristefano C, Zuppardo RA, Azzolini F, Passaretti S, Testoni PA. Transoral incisionless fundoplication with Medigus ultrasonic surgical endostapler (MUSE) for the treatment of gastro-esophageal reflux disease: outcomes up to 3 years. Surg Endosc. 2022 Jul;36(7):5023-5031. doi: 10.1007/s00464-021-08860-w. Epub 2021 Nov 19.
citation: Testoni PA, Testoni S, Mazzoleni G, Pantaleo G, Cilona MB, Distefano G, Fanti L, Antonelli M, Passaretti S. Transoral incisionless fundoplication with an ultrasonic surgical endostapler for the treatment of gastroesophageal reflux disease: 12-month outcomes. Endoscopy. 2020 Jun;52(6):469-473. doi: 10.1055/a-1124-3187. Epub 2020 Mar 18.