Endoscopic Full Thickness Plication (GERD-X) for the Treatment of PPI Dependent GERD:

Gastro Esophageal Reflux Disease Clinical Trial

Official title:

Endoscopic Full Thickness Plication (GERD-X) for the Treatment of PPI Dependent GERD: Randomized, Double Blinded, Sham Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03322553
• Other study ID #: GERDX01
• Status: Completed
• Phase: N/A
• Start date: November 15, 2017
• Est. completion date: December 30, 2019

Study information

• Verified date: October 2018
• Source: Asian Institute of Gastroenterology, India
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Gastro-esophageal reflux disease (GERD) is a common gastrointestinal disorder with a significant proportion of patients becoming dependent on proton pump inhibitor (PPI) therapy. Long term use of PPI therapy can be associated with side effects such as osteoporosis, small intestinal bacterial overgrowth and renal failure. Moreover, some of the patients might be reluctant to take PPIs for long duration and prefer surgery over pharmacotherapy. Endoscopic plication (GERD-X) is an alternative and less invasive procedure compared to laparoscopic fundoplication for the treatment of GERD. In endoscopic plication, transmural sutures are applied at the gastro-esophageal (GE) junction thereby reconstructing the gastric cardia and accentuating the valvular mechanism to prevent reflux. Only few trials have evaluated the efficacy of endoscopic plication technique and reported encouraging results. In this study we aim to evaluate the efficacy of a similar endoscopic technique but with application of two transmural sutures in randomized controlled method.

Description:

Patients screening and inclusion:

The study will be conducted over 6-month period. Data of patients presenting with PPI dependent GERD will be recorded and maintained. At initial screening, GERD health related quality of life questionnaire (GERD HRQL) and requirement of anti-secretory medicines (detailed drug history) will be assessed along with gastroscopy. All anti-secretory medicines will be stopped for 7 days and GERD HRQL will be reassessed off drugs. Esophageal high resolution manometry with 24-h pH impedance monitoring will be done on the 8th day after stopping medicines. Basal lower esophageal sphincter (LES) pressure, esophageal motility pattern, 24-h esophageal acid exposure, non acidic bolus reflux, number of reflux episodes, DeMeester score, symptom index and symptom association probability would be assessed. Those patients with pathologic esophageal acid exposure (esophageal pH <4 for >4.2% of 24-h period) will be included in the trial. Patients will then be randomly assigned by a computer to either GERD-X or sham procedure with a target ratio of 1:1. The patient, principle investigator and the study coordinators would be blinded to the treatment assignment.

Intervention:

In patients allocated to endoscopic plication, endoscopic full-thickness plication will be performed using the GERDX® system. All procedures will be performed under general anesthesia. Savary-guidewire will be placed into the stomach using a gastroscope. The GERDX® system will be introduced over the guidewire and into the stomach. The subsequent procedure will be performed as described in previous studies, using a similar device (NDO Plicator). According to study protocol, at least 2 pretied transmural pledgeted sutures will be deployed to achieve a tight closure of GE junction around the endoscope. In sham procedure, identical technique will be followed by positioning the plicator 1cm below the GE junction but sutures will not be deployed.

Post intervention monitoring:

Immediately after the intervention, patients would be placed on soft diet and on demand analgesics for 5 days. Twice daily PPI will be given for all patients and would be stopped after 7 days. Thereafter, if patient experiences reflux symptoms, sucralfate, H2 blocker and PPI would be started sequentially in case of no response to the former drug after a period of 7days of therapy on each drug. Requirement and reintroduction of drugs will be enquired over phone and recorded appropriately.

Follow up:

Follow up visits will be carried out at 3, 6 and 12 months. During each visit, gastroscopy will be done to assess the gastro-esophageal junction along with evaluation of GERD HRQL and requirement of PPI. At 3 months post intervention, esophageal manometry and 24-h pH impedance monitoring would be performed.

Primary outcomes:

Improvement in GERD HRQL by more than 50% from baseline at 3 months

Secondary outcomes:

Improvement in GERD HRQL at 3, 6 and 12 months Improvement in symptom score and requirement of PPI at 3, 6 and 12 months Improvement in esophageal acid exposure and lower esophageal sphincter pressure at 3 months

Statistical Analysis The trial was designed to have a 90% power to detect a difference in GERD-HRQL post intervention at 5% level of significance.

The rate of improvement in GERD-HRQL for sham group is 35% and for active group is 70 %. A sample size of 38 is required for each group to achieve a statistical power of 80% at 5% type I error.

Statistical methods Continuous data will be expressed as median and inter-quartile range (IQR). Frequency will be expressed as percentage (%). Continuous and categorical data between active and sham groups will be compared using Mann-Whitney U test and Chi-square test, with Yates' correction as applicable, respectively. P values below 0.05 will be considered significant.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: December 30, 2019
• Est. primary completion date: August 30, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Patients (between 18 to 60 years of age) with PPI dependent GERD and pathologic esophageal acid exposure as documented by percentage time esophageal pH less than 4 of more than 4.2% on pH-metry during 24-h period while off PPI

• Patients who are willing to pay the expenses of the GERD-X procedure

Exclusion Criteria:

• Large Hiatal hernia >3cm

• Gr C/D esophagitis

• Lower esophageal sphincter (LES) pressure <5 or >15 mm Hg

• Paraesophageal hernia

• GE flap valve grade IV (Hill's classification)

• Barretts esophagus

• Esophageal dysmotility

• ASA physical status >II

• Previous esophageal or gastric surgery

• Pregnancy

Related Conditions & MeSH terms

• Gastro Esophageal Reflux Disease
• Gastroesophageal Reflux

Intervention

Device:
• GERD-X
Endoscopic full-thickness plication will be performed using the GERDX® system. All procedures will be performed under general anesthesia. Savary-guidewire will be placed into the stomach using a gastroscope. The GERDX® system will be introduced over the guidewire into the stomach and retroflexed. The GE junction will be visualized using another slim endoscope passed through a channel present in the GERD-X device. According to study protocol, at least 2 pretied transmural pledgeted sutures will be deployed to achieve a tight closure of gastro-esophageal junction around the GERD-X device.

Locations

Country	Name	City	State
India	Asian institute of Gastroenterology	Hyderabad	Telangana

Sponsors (1)

Lead Sponsor	Collaborator
Asian Institute of Gastroenterology, India

Country where clinical trial is conducted

India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Improvement in GERD	Improvement in GERD HRQL by more than 50% from baseline at 3 months; GERD - Health Related Quality of Life Questionnaire (GERD-HRQL) : Total Score: Calculated by summing the individual scores toquestions 1-15 Greatest possible score ( worst symptoms)= 75 Lowest possible score ( no symptoms)= 0; Heartburn Score: Calculated by summing the individual scores to questions 1-6 .; Worst heartburn symptoms = 30 No heartburn symptoms= 0 Scores of = 12 with each individual question not exceeding 2 indicate heartburn elimination.; Regurgitation Score: Calculated by summing the individual scores to questions10-15.; Worst regurgitation symptoms = 30 No regurgitation symptoms = 0 Scores of = 12 with each individual question not exceeding 2 indicate regurgitation elimination.	3months
Secondary	Improvement in GERD overall symptom and quality of life score	Improvement in GERD HRQL at 3, 6 and 12 months; GERD - Health Related Quality of Life Questionnaire (GERD-HRQL) : Total Score: Calculated by summing the individual scores toquestions 1-15 Greatest possible score ( worst symptoms)= 75 Lowest possible score ( no symptoms)= 0; Heartburn Score: Calculated by summing the individual scores to questions 1-6 .; Worst heartburn symptoms = 30 No heartburn symptoms= 0 Scores of = 12 with each individual question not exceeding 2 indicate heartburn elimination.; Regurgitation Score: Calculated by summing the individual scores to questions10-15.; Worst regurgitation symptoms = 30 No regurgitation symptoms = 0 Scores of = 12 with each individual question not exceeding 2 indicate regurgitation elimination.	12 months
Secondary	Improvement in GERD symptom sub-score	Improvement in GERD symptom (heartburn and regurgitation) score at 3, 6 and 12 months; GERD - Health Related Quality of Life Questionnaire (GERD-HRQL) : Total Score: Calculated by summing the individual scores toquestions 1-15 Greatest possible score ( worst symptoms)= 75 Lowest possible score ( no symptoms)= 0; Heartburn Score: Calculated by summing the individual scores to questions 1-6 .; Worst heartburn symptoms = 30 No heartburn symptoms= 0 Scores of = 12 with each individual question not exceeding 2 indicate heartburn elimination.; Regurgitation Score: Calculated by summing the individual scores to questions10-15.; Worst regurgitation symptoms = 30 No regurgitation symptoms = 0 Scores of = 12 with each individual question not exceeding 2 indicate regurgitation elimination.	12 months
Secondary	Requirement of PPI	Requirement of PPI for control of symptoms at 3, 6 and 12 months; Heartburn and Regurgitation questionnaire; 0 =No symptom; 1 =Symptoms noticeablebut not bothersome 2=S ymptoms noticeableand bothersome but noteve ry day 3 =Symptoms bothersome every day 4 =Symptoms affect daily activity 5 =Symptoms are incapacitating to do daily activities	12 months
Secondary	Improvement in oesophageal acidification	Improvement in oesophageal acid exposure at 3 months; pH more than 4 of more than 4.2%	3 months
Secondary	Improvement in lower oesophageal sphincter pressure	Improvement in lower oesophageal sphincter pressure at 3 months; Lower Esophageal Sphincter pressure > 15 mm Hg	3 months