Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-line Helicobacter pylori treatment: a multicentre randomised trial in Japan

Abstract

Objective: To date, no randomised trials have compared the efficacy of vonoprazan and amoxicillin dual therapy with other standard regimens for Helicobacter pylori treatment. This study aimed to investigate the efficacy of the 7-day vonoprazan and low-dose amoxicillin dual therapy as a first-line H. pylori treatment, and compared this with vonoprazan-based triple therapy.

Design: This prospective, randomised clinical trial was performed at seven Japanese institutions. Patients with H. pylori-positive culture test and naive to treatment were randomly assigned in a 1:1 ratio to either VA-dual therapy (vonoprazan 20 mg+amoxicillin 750 mg twice/day) or VAC-triple therapy (vonoprazan 20 mg+amoxicillin 750 mg+clarithromycin 200 mg twice/day) for 7 days, with stratification by age, sex, H. pylori antimicrobial resistance and institution. Eradication success was evaluated by ¹³C-urea breath test at least 4 weeks after treatment.

Results: Between October 2018 and June 2019, 629 subjects were screened and 335 were randomised. The eradication rates of VA-dual and VAC-triple therapies were 84.5% and 89.2% (p=0.203) by intention-to-treat analysis, respectively, and 87.1% and 90.2% (p=0.372) by per-protocol analysis, respectively. VA-dual was non-inferior to VAC-triple in the per-protocol analysis. The eradication rates in strains resistant to clarithromycin for VA-dual were significantly higher than those for VAC-triple (92.3% vs 76.2%; p=0.048). The incidence of adverse events was equal between groups.

Conclusion: The 7-day vonoprazan and low-dose amoxicillin dual therapy provided acceptable H. pylori eradication rates and a similar effect to vonoprazan-based triple therapy in regions with high clarithromycin resistance.

Trial registration number: UMIN000034140.

Keywords: antibiotics - clinical trials; clinical trials; gastric inflammation; helicobacter pylori - treatment.

Figure 1

Flow chart of patient enrolment. ITT, intention-to-treat; PP, per protocol; VA-dual, vonoprazan and amoxicillin dual therapy; VAC-triple, vonoprazan, amoxicillin and clarithromycin triple therapy.

Figure 2

Eradication rates of each therapy groups in the presence of clarithromycin resistance in PP population. CLA, clarithromycin; PP, per protocol; VA-dual, vonoprazan and amoxicillin dual therapy; VAC-triple, vonoprazan, amoxicillin and clarithromycin triple therapy.

Figure 3

Eradication rates of each therapy groups according to MIC value of amoxicillin in PP population. AMO, amoxicillin; MIC, minimal inhibitory concentration; PP, per protocol; VA-dual, vonoprazan and amoxicillin dual therapy; VAC-triple, vonoprazan, amoxicillin and clarithromycin triple therapy.