Fexuprazan vs esomeprazole for endoscopic submucosal dissection-induced gastric ulcer healing: A double-blind randomized controlled trial

doi:10.3748/wjg.124419

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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Randomized Controlled Trial

Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Gastroenterol. Jan 14, 2027; 33(2): 124419
Published online Jan 14, 2027. doi: 10.3748/wjg.124419

Fexuprazan vs esomeprazole for endoscopic submucosal dissection-induced gastric ulcer healing: A double-blind randomized controlled trial

Hye Kyung Hyun, Jin Ho Hwang, Nak-Hoon Son, So Hyeon Gwon, Da Hyun Jung, Cheal Wung Huh

Hye Kyung Hyun, Jin Ho Hwang, Cheal Wung Huh, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin 16995, Gyeonggi-do, South Korea

Nak-Hoon Son, So Hyeon Gwon, Department of Statistics, Keimyung University, Daegu 42601, South Korea

Da Hyun Jung, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, South Korea

Co-corresponding authors: Da Hyun Jung and Cheal Wung Huh.

Author contributions: Hyun HK, Jung DH, and Huh CW contributed to the design of the study, performance of the endoscopic procedures, and the data acquisition; Hyun HK and Hwang JH contributed to the study execution and the data collection; Hyun HK, Son NH, Gwon SH and Huh CW contributed to the statistical analysis and the data interpretation; Hyun HK contributed to the manuscript drafting; Hyun HK, Hwang JH, Son NH, Gwon SH, Jung DH and Huh CW contributed to the critical revision of the manuscript for important intellectual content. Jung DH and Huh CW contributed equally to this work as co-corresponding authors.

AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.

Institutional review board statement: This study was approved by the Institutional Review Boards of Yongin Severance Hospital, No. 9-2023-0259 and Severance Hospital, No. 4-2024-0167.

Clinical trial registration statement: This study was registered at the Clinical Research Information Service, a primary registry of the World Health Organization International Clinical Trials Registry Platform, No. KCT0009356. URL: https://cris.nih.go.kr.

Informed consent statement: All study participants or their legal guardians provided informed written consent about personal and medical data collection prior to study enrolment.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.

Data sharing statement: Deidentified individual participant data that underlie the reported results will be made available beginning 6 months and ending 5 years after publication of this article. Data to be shared include the deidentified dataset of randomized patients with baseline characteristics, ulcer measurements at all time points, endoscopic findings, and safety outcomes. The study protocol and the statistical analysis plan are also available. Data will be made available to researchers who provide a methodologically sound proposal, approved by an independent review committee. Proposals should be directed to the corresponding authors (huhcw@yuhs.ac and jungdh@yuhs.ac); to gain access, data requestors will need to sign a data access agreement.

Corresponding author: Cheal Wung Huh, MD, PhD, Associate Professor, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Dongbaekjukjeon-daero Road, Giheung-gu District, Yongin 16995, Gyeonggi-do, South Korea. huhcw@yuhs.ac

Received: June 16, 2026
Revised: August 24, 2026
Accepted: October 23, 2026
Published online: January 14, 2027
Processing time: 144 Days and 10.3 Hours

Abstract

BACKGROUND

Endoscopic submucosal dissection (ESD) induces large artificial gastric ulcers requiring acid-suppressive therapy, but high-quality evidence comparing potassium-competitive acid blockers (P-CABs) with proton pump inhibitors is limited. We hypothesized that fexuprazan, a novel P-CAB, would achieve a higher complete healing rate of ESD-induced gastric ulcers than esomeprazole.

AIM

To evaluate the efficacy and safety of fexuprazan vs esomeprazole in the healing of ESD-induced gastric ulcers.

METHODS

In this multicenter, double-blind, double-dummy, parallel-group superiority randomized controlled trial, patients undergoing ESD for gastric neoplasms received fexuprazan 40 mg or esomeprazole 40 mg once daily for 8 weeks. The primary endpoint was the complete healing rate at 8 weeks, analyzed in both modified intention-to-treat (mITT) and per-protocol (PP) populations. Secondary endpoints included the ulcer shrinkage rate and delayed bleeding. The model-estimated time to a 99% reduction in ulcer area was compared as an exploratory endpoint.

RESULTS

Of 132 randomized patients, 128 received at least one dose of study medication and were included in the mITT analysis; 107 were included in the PP analysis. In the PP analysis, the 8-week complete healing rate was significantly higher with fexuprazan [90.2% vs 75.0%; risk difference (RD): 15.2%, 95% confidence interval (CI): 1.2-29.2; P = 0.040]; the mITT analysis showed a directionally consistent but non-significant difference (73.4% vs 65.6%; RD: 7.8%, 95%CI: -8.1 to 23.7; P = 0.337). Ulcer shrinkage rates at 4 weeks and 8 weeks were significantly greater with fexuprazan (both P = 0.049). In exploratory analysis, the model-estimated time to a 99% reduction in ulcer area was shorter with fexuprazan (40.31 days vs 47.22 days; P = 0.045), particularly among patients with large baseline ulcers (≥ 800 mm²). Safety was comparable between groups.

CONCLUSION

In the pre-specified PP analysis, fexuprazan achieved a significantly higher 8-week complete healing rate than esomeprazole, with comparable safety. Exploratory analysis suggested shorter model-estimated healing time in large ulcers, warranting larger trials.

Keywords: Fexuprazan; Potassium-competitive acid blocker; Esomeprazole; Endoscopic submucosal dissection; Gastric ulcer; Randomized controlled trial

Core Tip: This double-blind, double-dummy randomized controlled trial compared the potassium-competitive acid blocker fexuprazan with the proton pump inhibitor esomeprazole for the healing of artificial gastric ulcers after endoscopic submucosal dissection. Ulcer healing was assessed endoscopically at 4 weeks and 8 weeks. Fexuprazan achieved a significantly higher complete healing rate at 8 weeks in the pre-specified PP analysis (90.2% vs 75.0%) and greater ulcer shrinkage at both time points, although the difference was not significant in the modified intention-to-treat population. In an exploratory analysis, the model-estimated healing time was shorter with fexuprazan, particularly for large baseline ulcers (≥ 800 mm²). The safety profile was comparable between groups.