Seven-day vonoprazan and low-dose amoxicillin dual therapy as first-lineHelicobacter pyloritreatment: a multicentre randomised trial in Japan

Abstract

ObjectiveTo 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.DesignThis 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.ResultsBetween 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.ConclusionThe 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 numberUMIN000034140.

Efficacy and safety of a new rifabutin‐based triple therapy with vonoprazan for refractoryHelicobacter pyloriinfection: A prospective single‐arm study

“…This is likely due to use of vonoprazan as a substitute for PPIs, which reportedly enhances the therapeutic efficacy of CLR‐ and STFX‐based H pylori eradication regimens by increasing gastric pH 33‐35 . Recent reports utilizing vonoprazan in dual therapy with AMX also showed very high eradication rate in the first‐line therapy, suggesting the unnecessity of second antibiotic 36,37 . Thus, sufficient acid suppression achieved by vonoprazan would be one of important factors for successful eradication of refractory H pylori 38 .…”

Lack of significant differences between gastrointestinal tract microbial population structure of Helicobacter pylori‐infected subjects before and 2 years after a single eradication event

“…56,57 Alternatives to triple eradication therapy include bismuth quadruple therapy, concomitant therapy, sequential therapy, 4 and recently introduced vonoprazan therapy. 58,59 While concomitant and bismuth quadruple therapy have showed longterm perturbations of the gut microbiome, 47 vonoprazan therapy supplemented by probiotics has been shown to improve the rate of eradication and potentially aids the maintainment of species diversity within the gut microbiome. 60 Although a number of studies have identified vonoprazan as effective eradication strategy, [59][60][61] study evaluating the effect of vonoprazan monotherapy on the gut microbiome revealed stimulated lipopolysaccharide biosynthesis thus increasing the risk of enteric infection.…”

“…58,59 While concomitant and bismuth quadruple therapy have showed longterm perturbations of the gut microbiome, 47 vonoprazan therapy supplemented by probiotics has been shown to improve the rate of eradication and potentially aids the maintainment of species diversity within the gut microbiome. 60 Although a number of studies have identified vonoprazan as effective eradication strategy, [59][60][61] study evaluating the effect of vonoprazan monotherapy on the gut microbiome revealed stimulated lipopolysaccharide biosynthesis thus increasing the risk of enteric infection. 62 In general, adverse events are common in combinatorial therapies, thereof vonoprazan therapy accompanied by probiotics might be promising strategy in H pylori eradication, especially in regions with high resistance rates to clarithromycin.…”

Influence of clarithromycin on the bactericidal effect of amoxicillin in patients infected with clarithromycin-resistant strains of H. pylori

“…The eradication rates attained by a proton pump inhibitor (PPI), amoxicillin and clarithromycin were reportedly very low in patients infected with clarithromycin-resistant strains of H. pylori ,5 6 although amoxicillin-resistant strains of H. pylori are rare in Japan. The present study by Suzuki et al 1 accounts for the poor eradication rates by the triple therapy with a PPI, amoxicillin and clarithromycin in patients infected with clarithromycin-resistant strains of H. pylori . These clinical studies have suggested that clarithromycin not only does not work as antibiotics, but also has an adverse effect on the action of other antibiotics in cases infected with clarithromycin-resistant strains of H. pylori .…”

“…We read the manuscript written by Suzuki et al 1 with interest. They reported that the eradication rate of Helicobacter pylori attained by the dual therapy with vonoprazan and amoxicillin (VA-Dual) was almost the same as that attained by the triple therapy with vonoprazan, amoxicillin and clarithromycin (VAC-Triple), as previously reported by us 2.…”