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

NCT ID: NCT03322553

Last Updated: 2020-01-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-15
• Study Completion Date: 2019-12-30

Brief 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.

Detailed 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.

Conditions

Gastro Esophageal Reflux Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Plication group

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 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 GE junction around the GERD-X device

Group Type: EXPERIMENTAL

GERD-X

Intervention Type: DEVICE

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.

Sham Group

In sham procedure, identical technique will be followed by positioning the plicator inside the stomach but sutures will not be applied.

Group Type: SHAM_COMPARATOR

GERD-X

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Asian Institute of Gastroenterology, India

OTHER

Sponsor Role: lead

Responsible Party

Rakesh K

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dr. D. Nageshwar Reddy, MBBS

Role: STUDY_DIRECTOR

Asian Institute of Gastroenterology

Locations

Asian institute of Gastroenterology

Hyderabad, Telangana, India

Countries

India

References

Kalapala R, Karyampudi A, Nabi Z, Darisetty S, Jagtap N, Ramchandani M, Gupta R, Lakhtakia S, Goud R, Venkat Rao G, Sharma P, Reddy DN. Endoscopic full-thickness plication for the treatment of PPI-dependent GERD: results from a randomised, sham controlled trial. Gut. 2022 Apr;71(4):686-694. doi: 10.1136/gutjnl-2020-321811. Epub 2021 Apr 13.

Reference Type: DERIVED

PMID: 33849942 (View on PubMed)

Other Identifiers

GERDX01

Identifier Type: -

Identifier Source: org_study_id