Clinical Trials Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2024; 30(48): 5152-5161
Published online Dec 28, 2024. doi: 10.3748/wjg.v30.i48.5152
Efficacy and safety of rebamipide/nizatidine in patients with erosive gastritis: A randomized, multicenter, phase 4 study
Donghoon Kang, Myung-Gyu Choi, Ki-Nam Shim, Hye-Kyung Jung, Seung-Joo Nam, Jung Ho Park, Sang Gyun Kim, Nam-Hoon Kim, Su Jin Hong, Tae Joo Jeon, Jae Il Chung, Hang Lak Lee, Ju Yup Lee, Tae Oh Kim, Chang Min Lee, Sun Moon Kim, Jeong-Hwan Kim, Jang Eon Kim, Jeong Seop Moon, Ho Dong Kim, Wan-Sik Lee, Hong Jun Park
Donghoon Kang, Myung-Gyu Choi, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul 06591, South Korea
Ki-Nam Shim, Department of Internal Medicine, Ewha Womans University Seoul Hospital, Gastroenterology and Hepatology Center, Seoul 07985, South Korea
Hye-Kyung Jung, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Seoul 07985, South Korea
Seung-Joo Nam, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon 24289, South Korea
Jung Ho Park, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul 03181, South Korea
Sang Gyun Kim, Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul 03080, South Korea
Nam-Hoon Kim, Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang 10380, South Korea
Su Jin Hong, Department of Internal Medicine, Digestive Disease Center, Soonchunhyang University Bucheon Hospital, Bucheon 31538, South Korea
Tae Joo Jeon, Department of Internal Medicine, Inje University College of Medicine, Sanggye Paik Hospital, Seoul 01757, South Korea
Jae Il Chung, Department of Gastroenterology, Sahmyook Medical Center, Seoul 02500, South Korea
Hang Lak Lee, Department of Internal Medicine, Hanyang University College of Medicine, Seoul 04763, South Korea
Ju Yup Lee, Department of Internal Medicine, Keimyung University School of Medicine, Daegu 42601, South Korea
Tae Oh Kim, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan 48108, South Korea
Chang Min Lee, Department of Internal Medicine, Gyeongsang National University School of Medicine, Gyeongsang National University Hospital, Jinju 52727, South Korea
Sun Moon Kim, Department of Internal Medicine, Konyang University Hospital, Daejeon 35365, South Korea
Jeong-Hwan Kim, Gastroenterology Center, Konkuk University Medical Center, Seoul 05030, South Korea
Jang Eon Kim, Department of Gastroenterology, Seoul Medical Center, Seoul 02053, South Korea
Jeong Seop Moon, Department of Gastroenterology, Inje University Busan Paik Hospital, Busan 47392, South Korea
Ho Dong Kim, Department of Gastroenterology, St. Carollo Hospital, Sooncheon 57931, South Korea
Wan-Sik Lee, Division of Gastroenterology, Department of Internal Medicine, Chonnam Medical University Hwasun Hospital, Hwasun 58128, South Korea
Hong Jun Park, Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju 26426, South Korea
Author contributions: Choi MG contributed to the study concept and design; Choi MG, Shim KN, Jung HK, Nam SJ, Park JH, Kim SG, Kim NH, Hong SJ, Jeon TJ, Chung JI, Lee HL, Lee JY, Kim TO, Lee CM, Kim SM, Kim JH, Kim JE, Moon JS, Kim HD, Lee WS, Park HJ participated in the data acquisition in each institute; Kang D drafted the manuscript.
Supported by the Daewoong Pharmaceutical Co., Ltd. (Seoul, Korea).
Institutional review board statement: This trial was conducted following the principles of Good Clinical Practice and the Declaration of Helsinki. The study protocol was approved by the Institutional Review Board of each of the participating institutions including Seoul St. Mary’s Hospital (IRB number: KC21MSDV0559).
Clinical trial registration statement: This trial was registered as a standard, randomized clinical trial (ClinicalTrials.gov: NCT05072938).
Informed consent statement: Upon enrolment, written informed consent was obtained from all the participants.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data shown in this article are available from the corresponding authors upon a reasonable request (choim@catholic.ac.kr).
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Myung-Gyu Choi, MD, PhD, Professor, Department of Internal Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, 222 Banpodaero, Seoul 06591, South Korea. choim@catholic.ac.kr
Received: June 20, 2024
Revised: October 2, 2024
Accepted: November 11, 2024
Published online: December 28, 2024
Processing time: 161 Days and 22.8 Hours
Abstract
BACKGROUND

For the treatment of gastritis, rebamipide, a mucoprotective agent, and nizatidine, a gastric acid suppressant, are commonly employed individually.

AIM

To compare the efficacy of Mucotra® SR (rebamipide 150 mg) and Axid® (nizatidine 150 mg) combination therapy with the sole administration of Axid® in managing erosive gastritis.

METHODS

A total of 260 patients diagnosed with endoscopically confirmed erosive gastritis were enrolled in this open-label, multicenter, randomized, phase 4 clinical trial, allocating them into two groups: Rebamipide/nizatidine combination twice daily vs nizatidine twice daily for 2 weeks. The full-analysis set analysis encompassed 239 patients (rebamipide/nizatidine, n = 121; nizatidine, n = 118), while the per-protocol analysis included 218 patients (n = 110 vs 108). Post-treatment assessments comprised primary (erosion improvement rate) and secondary (erosion and edema cure rates, erythema improvement rates, hemorrhage, and gastrointestinal symptoms) endpoints. Furthermore, drug-related adverse effects were evaluated.

RESULTS

Primary efficacy assessment showed a statistically significant improvement rate in mucosal erosions in the combination group compared to the control group in the full-analysis set (rebamipide/nizatidine 62.0%, nizatidine 49.2%, P = 0.046), with a similar trend noted in the per-protocol analysis (62.7% vs 50.0%, P = 0.058). Both groups were effective in curing erosion and edema and improvement of bleeding, erythema, and gastrointestinal symptoms, whereas no inter-group differences were noted. When confined to the participants with gastritis symptoms, improvement of erosion was more optimal in the combination group (63.0% vs 49.5%, P = 0.046). No adverse events related to the drugs were observed.

CONCLUSION

Rebamipide/nizatidine combination is effective in treatment of erosive gastritis.

Keywords: Gastritis; Erosive gastritis; Combination therapy; Rebamipide; Nizatidine

Core Tip: This multicenter, randomized phase 4 trial compared the efficacy and safety of rebamipide/nizatidine combination therapy vs nizatidine monotherapy in treating erosive gastritis. The study demonstrated that the combination therapy significantly improved mucosal erosion healing compared to monotherapy, highlighting the potential benefit of combining an acid suppressant with a mucoprotective agent. While both treatment groups showed positive outcomes in managing symptoms, no significant differences in adverse events were observed. These findings suggest that combination therapy may offer a more effective approach for patients with erosive gastritis.