Multicenter, double-blind, sham endoscopy-controlled, randomized trial evaluating the efficacy of anti-reflux mucosal ablation for the treatment of gastro-esophageal reflux disease.

Background and aims Antireflux mucosal ablation (ARMA) is a novel endoscopic technique for gastro-esophageal reflux disease (GERD) but has only been assessed in non-controlled studies. The objective of this randomized, controlled study was to evaluate its efficacy in patients with proton pump inhibitor (PPI)-responsive GERD. Patients and methods We conducted a double-blind, sham endoscopy-controlled, randomized trial across 12 Spanish hospitals. Adults with PPI-responsive GERD and abnormal esophageal acid exposure (AET>6%) were randomly assigned (1:1) to receive ARMA or sham endoscopy. The primary outcome was clinical success at 12 months, defined as a ≥50% reduction in the GERD-HRQL score. Inability to discontinue PPIs for symptom assessment was considered a treatment failure. Secondary outcomes included PPI discontinuation, AET, manometric parameters, mucosal healing, and adverse events. Results Of 186 patients screened, 60 were included (ARMA: 31; sham: 29). At 12 months, clinical success was achieved in 16/31 (51.6%) patients in the ARMA group and in 11/29 (37.9%) in the sham group (p=0.29) (risk ratio 1.36; 95% CI 0.76 to 2.42). No significant differences were observed in PPI discontinuation, AET, manometric findings or mucosal healing. Postprocedural pain (27.3% vs 3.3%) and dysphagia (45.5% vs 10%) occurred more frequently in the ARMA group. No severe adverse events were recorded. Conclusions ARMA was not superior to sham endoscopy in improving GERD-related quality of life at 12 months in patients with PPI-responsive GERD and was associated with a higher incidence of adverse events. These findings do not support its implementation in routine clinical practice. ClinicalTrials.gov registration number: NCT04711655.