Endoscopic full-thickness plication for the treatment of PPI-dependent GERD: results from a randomised, sham controlled trial

Abstract

Background: The majority of endoscopic antireflux procedures for GERD are cumbersome to use and randomised long-term data are sparse. We conducted such a trial to determine the efficacy and safety of a novel, easy to use endoscopic full-thickness fundoplication (EFTP) device in patients with GERD.

Design: Patients with proton pump inhibitor (PPI)-dependent GERD were randomised to either EFTP or a sham procedure in 1:1 ratio. The primary endpoint was ≥50% improvement in the health-related quality of life (GERD-HRQL) score at 3 months. Secondary end points included improvement in GERD-HRQL, reflux symptom scores, PPI usage, oesophageal acid exposure and reflux episodes and endoscopic findings at 3, 6 and 12 months.

Results: Seventy patients were randomised; 35 in each group with a median (IQR) age of 36 (29-42) years, 71.4% males. 70% had non-erosive reflux disease on endoscopy with a mean DeMeester score of 18.9 (±19.93). The mean (±SD) duration of EFTP procedure was 17.4 (±4) min. The primary end point was more frequently achieved in the EFTP group (65.7% vs 2.9%; p<0.001). Median (IQR) % improvement in GERD-HRQL was significantly higher in the EFTP group at 6 (81.4 (60.9-100.0) versus 8.0 (2.2-21.6); p<0.001) and 12 (92.3 (84.4-100.0) versus 9.1 (4.8-36.0); p<0.001) months. In the EFTP group, 62.8% patients were off-PPI at 12 months compared with 11.4% in the sham group (p<0.001). pH-metry parameters partially improved at 3 months, (n=70; total reflux episodes in EFTP arm and non-acid reflux episodes for EFTP vs sham) but not at 12 months (n=27); endoscopic oesophagitis was seen in 0% in the treatment (n=18) and 5 (29.4%) in the control group (n=17) at 12 months. No major procedure-related adverse events were encountered in either group.

Conclusion: EFTP using a novel device is safe and effective in improving quality of life in patients with PPI dependent mostly non-erosive reflux disease at short and long terms; objective parameters showed a limited response rate.

Trial registration number: NCT03322553.

Keywords: endoscopy; gastroesophageal reflux disease; quality of life.

Figure 1

GERDx device (A) with a control section, long shaft and two openable arms at the tip of the shaft; pretied pledget sutures are fastened to the arms (inset). (B) Retroflexion of the tip of the shaft with a rotatable tissue retractor between the arms facilitate the application of transmural sutures at the gastro-oesophageal junction.

Figure 2

Consolidated Standards of Reporting Trials flow diagram showing distribution of patients in the study. PPI, proton pump inhibitor; LESP, lower oesophageal sphincter pressure; GERDx, endoscopic full-thickness fundoplication.

Figure 3

Primary end point. The endoscopic full-thickness plication (EFTP; GERDx) group achieved ≥50% improvement in GERD-HRQL total score more frequently than the sham group at 3 months post intervention. GERD-HRQL, GERD health-related quality of life; GERDx or EFTP, endoscopic full-thickness fundoplication.

Figure 4

% improvement in GERD-HRQL total score. The EFTP (GERDx) group had significant improvement in the GERD-HRQL total score at 3, 6 and 12 months post intervention compared to the sham group. Error bars indicate 95% CI. Red and blue dots and asterisks represent outliers. GERD-HRQL, GERD health-related quality of life; GERDx or EFTP, endoscopic full-thickness fundoplication.

Figure 5

% improvement in reflux symptom scores. The EFTP (GERDx) group had significant improvement in heartburn and regurgitation scores at 3, 6 and 12 months post intervention compared to the sham group. Error bars indicate 95% CI. Red and blue dots and asterisks represent outliers. GERD-HRQL, GERD health-related quality of life; GERDx or EFTP, endoscopic full-thickness fundoplication.

Figure 6

Proton pump inhibitors (PPIs) dependency. The Kaplan-Meier survival analysis showed a significantly lower cumulative probability of PPI dependence in the EFTP (GERDx) group compared to the sham group over time after intervention. GERDx or EFTP, endoscopic full-thickness fundoplication.

Figure 7

24-hour reflux parameters at 3 months post intervention. Before and after plots showing significant reduction in total reflux episodes, but not acid exposure time in the EFTP (GERDx) group compared to the sham group. GERDx or EFTP, endoscopic full-thickness fundoplication.