Vonoprazan Dual or Triple Therapy Versus Bismuth-Quadruple Therapy as First-Line Therapy for Helicobacter pylori Infection: A Three-Arm, Randomized Clinical Trial

IF 4.3 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Helicobacter Pub Date : 2024-09-07 DOI:10.1111/hel.13133

Ka Shing Cheung, Tao Lyu, Zijie Deng, Shaowei Han, Li Ni, Juan Wu, Jing Tong Tan, Jian Qin, Ho Yu Ng, Wai K. Leung, Wai-Kay Seto

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Abstract

Background

We compared efficacy of vonoprazan-dual or triple therapies and bismuth-quadruple therapy for treatment-naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%.

Methods

This was an investigator-initiated, three-arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment-naïve HP-infected adults were randomly assigned to receive one of three 14-day regimens (1:1:1 ratio): vonoprazan-dual (VA-dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan-triple (VAC-triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth-quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4–6 weeks post-treatment by intention-to-treat (ITT) and per-protocol (PP) analysis (based on subjects who completed 14-day treatment and rechecked UBT). Bonferroni-adjusted p-value of <0.017 was used to determine statistical significance.

Results

A total of 298 subjects (mean age: 35.7 ± 8.4 years; male: 134 [45.0%]; VC-dual: 100, VAC-triple: 98, bismuth-quadruple: 100) were enrolled, and 292 (98.0%) had UBT rechecked. ITT analysis showed that both VA-dual (eradication rate of 96.0%) and VAC-triple therapies (95.9%) were noninferior to bismuth-quadruple therapy (92.0%) (difference: 4.0%, 95% CI: −2.9% to 11.5%, p < 0.001; and 3.9%, 95% CI: −3.1% to 11.5%, p < 0.001, respectively). PP analysis also revealed noninferiority (96.7% or 96.7% vs. 97.4%, with difference: −2.9% and −2.9%, p = 0.009 and 0.010, respectively). The frequency of adverse events was 39.0%, 56.1%, and 71.0% in VA-dual, VAC-triple, and bismuth-quadruple therapies, respectively.

Conclusions

VA-dual and VA-triple therapies are highly effective and noninferior to bismuth-quadruple therapy in Southern China. Given the lower adverse effects and fewer antibiotic use, VA-dual therapy is the preferred first-line treatment for HP infection.

Trial Registration

Chinese Clinical Trial Registry (No. ChiCTR2200056375). Registered on February 4, 2022, https://www.chictr.org.cn/showproj.aspx?proj=14131.

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沃诺普拉赞双重或三重疗法与铋剂-四重疗法作为幽门螺杆菌感染的一线疗法：三臂随机临床试验。

背景：在克拉霉素和左氧氟沙星耐药率大于30%的中国南方地区，我们比较了vonoprazan-二联或三联疗法和铋剂-四联疗法对未经治疗的幽门螺旋杆菌（HP）感染的疗效：这是一项由研究者发起的三臂随机临床试验。在2022年3月至2023年8月期间，接受过治疗的HP感染成人被随机分配到三种14天治疗方案（1:1:1比例）中的一种：vonoprazan-双联疗法（VA-双联疗法；vonoprazan 20 毫克，每天两次；阿莫西林 1 克，每天三次）、vonoprazan-三联疗法（VAC-三联疗法；vonoprazan 20 毫克/阿莫西林 1 克/克拉霉素 500 毫克，每天两次）或含铋剂、埃索美拉唑、四环素和甲硝唑的铋剂-四联疗法。主要结果是根除 HP 的非劣效性，通过治疗后 4-6 周的 UBT 评估，采用意向治疗 (ITT) 和每方案 (PP) 分析（基于完成 14 天治疗并复查 UBT 的受试者）。结果的 Bonferroni-adjusted p 值：共有 298 名受试者（平均年龄：35.7 ± 8.4 岁；男性：134 [45.0%]；VC-双联：100 人，VAC-三联：98 人，Bismuth-四联：100 人）入组：其中 292 人（98.0%）接受了 UBT 复查。ITT 分析显示，VA-双疗法（根除率为 96.0%）和 VAC-三联疗法（95.9%）均不劣于铋剂-四联疗法（92.0%）（差异为 4.0%，95% C%）：差异：4.0%，95% CI：-2.9% 至 11.5%，P在华南地区，VA-二联疗法和VA-三联疗法疗效显著，且不劣于铋剂-四联疗法。鉴于不良反应较少、抗生素用量较少，VA-二联疗法是治疗人乳头瘤病毒感染的首选一线疗法：试验注册：中国临床试验注册中心（编号：ChiCTR2200056375）。注册时间：2022年2月4日，https://www.chictr.org.cn/showproj.aspx?proj=14131。

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来源期刊

Helicobacter 医学-微生物学

CiteScore

8.40

自引率

9.10%

发文量

审稿时长

2 months

期刊介绍： Helicobacter is edited by Professor David Y Graham. The editorial and peer review process is an independent process. Whenever there is a conflict of interest, the editor and editorial board will declare their interests and affiliations. Helicobacter recognises the critical role that has been established for Helicobacter pylori in peptic ulcer, gastric adenocarcinoma, and primary gastric lymphoma. As new helicobacter species are now regularly being discovered, Helicobacter covers the entire range of helicobacter research, increasing communication among the fields of gastroenterology; microbiology; vaccine development; laboratory animal science.