Randomized Controlled Trial
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2025; 31(28): 109001
Published online Jul 28, 2025. doi: 10.3748/wjg.v31.i28.109001
Efficacy and safety of triple therapy with vonoprazan for Helicobacter pylori eradication: A multicenter, prospective, randomized controlled trial
Rong-Shuang Han, Jing-Wen Hao, Tong Wang, Zhi Xin, Guang-Xue Fan, Guo-Dong Wang, Miao-Miao Liu, Cheng-Xia Liu, Qiu-Zi Yang, Zheng-Wu Yang, Xiao-Yan Lv, Chao Zhang, Gang Bian, Jing Meng, Zhen-Qin Cui, Xiao-Jing Yun, Jian-Hua Cao, Shu-Hui Li, Jia-Feng Fan, Hong-Gang Ma, Feng-Yu Gao, Tao Mao, Zi-Bin Tian, Xiao-Hui Song, Ya-Nan Yu
Rong-Shuang Han, Jing-Wen Hao, Tao Mao, Zi-Bin Tian, Ya-Nan Yu, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong Province, China
Tong Wang, Department of Epidemiology and Health Statistics, Qingdao University, Qingdao 266071, Shandong Province, China
Zhi Xin, Department of Gastroenterology, Laixi People's Hospital, Qingdao 266600, Shandong Province, China
Guang-Xue Fan, Xiao-Hui Song, Department of Gastroenterology, The People's Hospital of Jimo, Qingdao 266299, Shandong Province, China
Guo-Dong Wang, Department of Gastroenterology, Changle People's Hospital, Weifang 262400, Shandong Province, China
Miao-Miao Liu, Department of Gastroenterology, The People's Hospital of Rongcheng, Weihai 264333, Shandong Province, China
Cheng-Xia Liu, Department of Gastroenterology and Hepatology, Binzhou Medical University Hospital, Binzhou 256600, Shandong Province, China
Qiu-Zi Yang, Department of Gastroenterology, The People's Hospital of Rizhao, Rizhao 276827, Shandong Province, China
Zheng-Wu Yang, Department of Gastroenterology, The Second Affiliated Hospital of Shandong First Medical University, Tai’an 271000, Shandong Province, China
Xiao-Yan Lv, Department of Gastroenterology, The People’s Hospital of Zouping, Binzhou 256200, Shandong Province, China
Chao Zhang, Department of Gastroenterology, Heze Municipal Hospital, Heze 274006, Shandong Province, China
Gang Bian, Department of Gastroenterology, The Affiliated Qingdao Third People's Hospital of Qingdao University, Qingdao 266041, Shandong Province, China
Jing Meng, Department of Gastroenterology, Rizhao Traditional Chinese Medicine Hospital, Rizhao 276800, Shandong Province, China
Zhen-Qin Cui, Department of Gastroenterology, Shengli Oilfield Central Hospital, Dongying 257034, Shandong Province, China
Xiao-Jing Yun, Department of Gastroenterology, The Second People's Hospital of Liaocheng, Liaocheng 252600, Shandong Province, China
Jian-Hua Cao, Department of Gastroenterology, Jinxiang People's Hospital, Jining 272200, Shandong Province, China
Shu-Hui Li, Department of Gastroenterology, Tengzhou Central People’s Hospital, Zaozhuang 277500, Shandong Province, China
Jia-Feng Fan, Department of Gastroenterology, Xiajin County People's Hospital, Dezhou 253200, Shandong Province, China
Hong-Gang Ma, Department of Gastroenterology, The People's Hospital of Linqing, Liaocheng 252600, Shandong Province, China
Feng-Yu Gao, Department of Gastroenterology, Shandong Provincial Maternal and Child Health Care Hospital, Jinan 250014, Shandong Province, China
Co-first authors: Rong-Shuang Han and Jing-Wen Hao.
Co-corresponding authors: Xiao-Hui Song and Ya-Nan Yu.
Author contributions: Han RS and Hao JW were responsible for writing the original article and organizing the data. Both authors have made crucial and indispensable contributions towards the completion of the project and thus qualified as the co-first authors of the paper. As co-corresponding authors, Yu YN and Song XH jointly oversaw experimental design, data interpretation, and manuscript preparation. Yu YN secured funding and supervised all project phases, including literature synthesis and initial manuscript submission with focus on the vonoprazan’s eradication rate. Song XH spearheaded data reanalysis with reinterpretation, figure generation and final manuscript submission with the focus on the drug interactions. Their collaborative synergy was critical to this publication. Zhang C, Liu CX, Gao FY, Wang GD, Bian G, Fan GX, Ma HG, Fan JF, Cao JH, Meng J, Liu MM, Yang QZ, Li SH, Mao T, Tian ZB, Lv XY, Yun XJ, Yang ZW, Xin Z, Cui ZQ contributed to patient recruitment and follow-up. Wang T was responsible for data analysis. All authors reviewed the manuscript and approved the final version of this report.
Supported by Qilu Health Outstanding Young Talent Cultivation Project, No. QDFY-3839.
Institutional review board statement: The study protocol was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University (No. QFYKYLL 916411920) and the Ethics Committees of all participating centers.
Clinical trial registration statement: This study has been registered at ClinicalTrials.gov (registration number: ChiCTR2200061000).
Informed consent statement: All the individuals who participated in this study provided their written informed consent 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: The data that support the findings of this study are available on request from the corresponding author.
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: Ya-Nan Yu, MD, Professor, Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao 266000, Shandong Province, China. yananyu@qdu.edu.cn
Received: April 30, 2025
Revised: May 25, 2025
Accepted: July 7, 2025
Published online: July 28, 2025
Processing time: 85 Days and 21 Hours
Abstract
BACKGROUND

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that relies on flagellar motility to colonize the stomach, damaging the gastric mucosa through various mechanisms and leading to various digestive disorders. Accurate assessment and precise treatment are essential in initial intensive therapy.

AIM

To investigate the efficacy and safety of a vonoprazan (VPZ)-based triple regimen for first-line eradication of H. pylori in China.

METHODS

This multicenter noninferior randomized controlled trial (June 2022 to November 2023) involved 524 H. pylori-positive patients across 19 centers in Shandong, China. Participants were randomized to 14-day esomeprazole/bismuth/amoxicillin/clarithromycin (EBAC), 14-day VPZ/amoxicillin/clarithromycin (VACa), or 10-day VPZ/amoxicillin/clarithromycin (VACb) - all administered twice daily. Primary outcomes (eradication rates) were assessed via intention-to-treat (ITT) and per-protocol (PP) analyses. Secondary endpoints included adverse events and adherence. Noninferiority testing and χ2 tests were used for statistical comparisons.

RESULTS

A total of 524 patients participated in this study. In ITT analysis, the eradication rates of the EBAC, VACa, and VACb groups were 72.6% (127/175), 88.0% (154/175), and 83.3% (145/174), respectively (P = 0.001). The difference in the eradication rate between the EBAC and VPCa groups was 15.4% [95% confidence interval (CI): 7.3-23.6, P < 0.001], and that between the EBAC and VACb groups was 10.8% (95%CI: 2.1-19.4, P = 0.018). In PP analysis, the eradication rates of the EBAC, VACa, and VACb groups were 81.4% (127/156), 93.9% (154/164), and 90.6% (145/160), respectively (P = 0.001). There was no significant difference in the incidence of adverse reactions among the three groups, which were 36.6%, 33.8% and 29.6%, respectively (P = 0.50).

CONCLUSION

VPZ-based triple therapies demonstrate noninferiority to 14-day bismuth-containing regimens, with the 10-day regimen showing comparable efficacy and similar adverse event rates.

Keywords: Helicobacter pylori; Vonoprazan triple therapy; Potassium-competitive acid blockers; Eradication rate; First-line therapy

Core Tip: This multicenter randomized controlled trial pioneered a head-to-head comparison of vonoprazan (VPZ)-based triple therapy (VPZ/amoxicillin/clarithromycin) against China’s standard 14-day bismuth quadruple regimen esomeprazole/bismuth/amoxicillin/clarithromycin (EBAC), while evaluating a novel 10-day VPZ regimen. Among 524 treatment-naïve patients, VPZ triple therapy demonstrated superior eradication rates vs EBAC in intention-to-treat and per-protocol analyses, achieving noninferiority thresholds. Adverse event incidence remained comparable, with the 10-day regimen showing the lowest rate. These findings establish VPZ triple therapy as an effective bismuth-free alternative, validating abbreviated 10-day regimens to enhance compliance without compromising efficacy.