Endoscopic Full Thickness Plication (GERD-X) for the Treatment of PPI Dependent GERD:
Condition: Gastro Esophageal Reflux Disease
MeSH terms: Gastroesophageal Reflux
Study type: Interventional

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.
    

Intervention name(s): GERD-X
Intervention type(s): Device
Intervention description(s): 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomized, Double blinded, sham controlled trial
Masking: Double (Participant, Investigator)
Primary purpose: Treatment