Multicenter, double-blind, sham endoscopy-controlled, randomized trial evaluating the efficacy of antireflux mucosal ablation for the treatment of gastroesophageal reflux disease

Abstract

Background Antireflux mucosal ablation (ARMA) is a novel endoscopic technique for gastroesophageal reflux disease (GERD) but has only been assessed in noncontrolled studies. The objective of this randomized controlled study was to evaluate its efficacy in patients with proton pump inhibitor (PPI)-responsive GERD.

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 time (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-Health-Related Quality of Life score. Inability to discontinue PPIs to allow symptom assessment was considered 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 patients (51.6 %) in the ARMA group and in 11 (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. 10.0 %) 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.

^‡ These authors contributed equally.

Publication History

Received: 03 August 2025

Accepted after revision: 29 December 2025

Accepted Manuscript online:
31 December 2025

Article published online:
10 February 2026

• References

• 1 Yadlapati R, Gyawali CP, Pandolfino JE. et al. AGA clinical practice update on the personalized approach to the evaluation and management of GERD: expert review. Clin Gastroenterol Hepatol 2022; 20: 984-994
• 2 de la Coba Ortiz C, Argüelles Arias F, Martín de Argila de Prados C. et al. Proton-pump inhibitors adverse effects: a review of the evidence and position statement by the Sociedad Española de Patología Digestiva. Rev Esp Enferm Dig 2016; 108: 207-224
• 3 Yadlapati R, Hungness ES, Pandolfino JE. Complications of antireflux surgery. Am J Gastroenterol 2018; 113: 1137-1147
• 4 Rodríguez de Santiago E, Albéniz E, Estremera-Arevalo F. et al. Endoscopic anti-reflux therapy for gastroesophageal reflux disease. World J Gastroenterol 2021; 27: 6601-6614
• 5 Inoue H, Tanabe M, de Santiago ER. et al. Anti-reflux mucosal ablation (ARMA) as a new treatment for gastroesophageal reflux refractory to proton pump inhibitors: a pilot study. Endosc Int Open 2020; 8: E133-E138
• 6 Sumi K, Inoue H, Manolokis AC. et al. Effect of anti-reflux mucosectomy (ARMS) for refractory GERD underwent 24-h pH-impedance (MII-pH) off PPI before and after ARMS. J Gastroenterol Hepatol 2018; 33 (Suppl. 04) 57
• 7 Rodríguez de Santiago E, Sanchez-Vegazo CT, Peñas B. et al. Antireflux mucosectomy (ARMS) and antireflux mucosal ablation (ARMA) for gastroesophageal reflux disease: a systematic review and meta-analysis. Endosc Int Open 2021; 9: E1740-E1751
• 8 Yeh J-H, Lee C-T, Hsu M-H. et al. Antireflux mucosal intervention (ARMI) procedures for refractory gastroesophageal reflux disease: a systematic review and meta-analysis. Therap Adv Gastroenterol 2022; 15: 17562848221094959
• 9 Hopewell S, Chan A-W, Collins GS. et al. CONSORT 2025 statement: updated guideline for reporting randomised trials. BMJ 2025; 389: e081123
• 10 Gyawali CP, Kahrilas PJ, Savarino E. et al. Modern diagnosis of GERD: the Lyon Consensus. Gut 2018; 67: 1351-1362
• 11 Cotton PB, Eisen GM, Aabakken L. et al. A lexicon for endoscopic adverse events: report of an ASGE workshop. Gastrointest Endosc 2010; 71: 446-454
• 12 Haseeb M, Glissen Brown JR, Hayat U. et al. Does transoral incisionless fundoplication (TIF. 2.0) improve atypical GERD symptoms? A systematic review and meta-analysis. . Gastrointest Endosc 2023; 97: 394-406
• 13 McCarty TR, Itidiare M, Njei B. et al. Efficacy of transoral incisionless fundoplication for refractory gastroesophageal reflux disease: a systematic review and meta-analysis. Endoscopy 2018; 50: 708-725
• 14 Cremonini F, Ziogas DC, Chang HY. et al. Meta-analysis: the effects of placebo treatment on gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2010; 32: 29-42
• 15 Tack J, Pandolfino JE. Pathophysiology of gastroesophageal reflux disease. Gastroenterology 2018; 154: 277-288
• 16 Spechler SJ, Hunter JG, Jones KM. et al. Randomized trial of medical versus surgical treatment for refractory heartburn. N Engl J Med 2019; 381: 1513-1523
• 17 Kalapala R, Karyampudi A, Nabi Z. et al. Endoscopic full-thickness plication for the treatment of PPI-dependent GERD: results from a randomised, sham controlled trial. Gut 2022; 71: 686-694
• 18 Bollschweiler E, Knoppe K, Wolfgarten E. et al. Prevalence of dysphagia in patients with gastroesophageal reflux in Germany. Dysphagia 2008; 23: 172-176
• 19 Zerbib F, Bredenoord AJ, Fass R. et al. ESNM/ANMS consensus paper: diagnosis and management of refractory gastro-esophageal reflux disease. Neurogastroenterol Motil 2021; 33: e14075
• 20 Shimamura Y, Inoue H, Tanabe M. et al. Clinical outcomes of anti-reflux mucosal ablation for gastroesophageal reflux disease: an international bi-institutional study. J Gastroenterol Hepatol 2024; 39: 149-156
• 21 Hernández MondragónOV, Zamarripa MottúRA, García ContrerasLF. et al. Clinical feasibility of a new antireflux ablation therapy on gastroesophageal reflux disease (with video). Gastrointest Endosc 2020; 92: 1190-1201
• 22 Kuipers T, Oude Nijhuis RAB, Pouw RE. et al. Antireflux mucosectomy for gastroesophageal reflux disease: efficacy and the mechanism of action. Endoscopy 2024; 56: 897-905
• 23 Lee AY, Kim SH, Cho JY. Comparative clinical feasibility of antireflux mucosectomy and antireflux mucosal ablation in the management of gastroesophageal reflux disease: retrospective cohort study. Dig Endosc 2024; 36: 1328-1337
• 24 Inoue H, Yamamoto K, Shimamura Y. et al. Pilot study on anti-reflux mucoplasty: Advancing endoscopic anti-reflux therapy for gastroesophageal reflux disease. Dig Endosc 2024; 36: 690-698