Efficacy and Safety of Vonoprazan and Amoxicillin Dual Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis

Digestion. 2023;104(4):249-261. doi: 10.1159/000529622. Epub 2023 Apr 4.


Introduction: Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication.

Methods: We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis.

Results: Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7-91.5% and 88.5% (95% CI: 83.2-93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97-1.10) and 1.02 (95% CI: 0.98-1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05-1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03-1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85-0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73-1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01).

Conclusions: The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.

Keywords: Adverse event; Cure rate; Dual therapy; Helicobacter pylori; Vonoprazan.

Publication types

  • Systematic Review
  • Meta-Analysis

MeSH terms

  • Amoxicillin / therapeutic use
  • Anti-Bacterial Agents / adverse effects
  • Clarithromycin / therapeutic use
  • Drug Therapy, Combination
  • Helicobacter Infections* / drug therapy
  • Helicobacter pylori*
  • Humans
  • Lansoprazole / pharmacology
  • Lansoprazole / therapeutic use
  • Omeprazole / pharmacology
  • Omeprazole / therapeutic use
  • Proton Pump Inhibitors / adverse effects
  • Pyrroles / adverse effects
  • Treatment Outcome


  • Amoxicillin
  • Clarithromycin
  • Anti-Bacterial Agents
  • 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine
  • Proton Pump Inhibitors
  • Pyrroles
  • Lansoprazole
  • Omeprazole

Grants and funding

This study was supported by the Natural Science Foundation of Shandong Province (ZR2020LZL003), the Key R&D Program of Shandong Province (2021ZLGX02), and the Clinical Research Center of Shandong University (2020SDUCRCA006). PRISMA 2009 Checklist: The guidelines of the PRISMA 2009 Statement have been adopted.