Comparison of Fexuprazan and Esomeprazole for the Control of Nocturnal Gastroesophageal Reflux Symptoms: A Randomized, Crossover Study

Abstract

Background/Aims: Nocturnal acid reflux disrupts sleep and impairs quality of life. Proton pump inhibitors provide insufficient suppression of nocturnal acid secretion, whereas fexuprazan offers prolonged acid suppression. We compared the efficacy of fexuprazan and esomeprazole in controlling nocturnal reflux. Methods: In a randomized and crossover study, patients received fexuprazan or esomeprazole daily for 4 weeks, followed by a washout and crossover to the alternate medication for another 4 weeks, with a final washout completing the sequence. Severity (scores 0-10), frequency, sleep disturbance, and medication preferences were evaluated. Results: Thirty-nine patients were enrolled and randomized to receive either fexuprazan (n = 20) or esomeprazole (n = 19) first. After the first treatment, fexuprazan reduced severity from 7.5 ± 1.7 to 1.4 ± 1.7 (81.3% decrease), versus 7.8 ± 1.5 to 2.8 ± 1.9 (64.1% decrease) with esomeprazole (P = 0.012). In patients with severe symptoms (scores ≥ 7), fexuprazan led to significantly greater improvement than esomeprazole (P = 0.008). Following the first washout, the second crossover treatment resulted in greater improvement in symptom severity with fexuprazan (P = 0.001). During the second washout, nocturnal symptoms severity and frequencies were better controlled with fexuprazan than with esomeprazole (P = 0.005 and 0.019). Patients who switched from esomeprazole to fexuprazan preferred fexuprazan (P = 0.018). Conclusions: Fexuprazan was more effective than esomeprazole in controlling nocturnal reflux symptom, particularly in patients with severe symptoms. Fexuprazan may offer a therapeutic advantage for patients with severe and persistent nocturnal reflux despite proton pump inhibitor therapy. © 2026 The Korean Society of Neurogastroenterology and Motility. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.