Efficacy of Three Amoxicillin Doses in Vonoprazan Dual Therapy for Helicobacter pylori Eradication: A Randomized Noninferiority Trial

Helicobacter. 2025 May-Jun;30(3):e70050. doi: 10.1111/hel.70050.

Abstract

Background: Limited research has explored the efficacy of reduced amoxicillin dosages in vonoprazan-amoxicillin (VA) dual therapy for Helicobacter pylori eradication in China, and this study aimed to assess the noninferiority of these lower dosages compared to the standard high dose (3 g/d).

Methods: This was a noninferiority study with a -10% margin. H. pylori-positive patients from 13 centers in Jiangsu Province, China, were randomly assigned in a 1:1:1 ratio to receive a 14-day treatment, consisting of vonoprazan (20 mg BID) and high-dose amoxicillin (1 g TID, HVA), medium-dose amoxicillin (1 g BID, MVA), or low-dose amoxicillin (0.5 g TID, LVA). The eradication rates, adverse events (AEs), and medication adherence were compared.

Results: From January 13, 2023 to July 6, 2024, a total of 900 patients were enrolled. According to the intention-to-treat (ITT) and per-protocol (PP) analyses, the eradication rates for HVA, MVA, and LVA groups were 93.2% and 93.2%, 91.6% and 91.5%, and 87.0% and 86.8%, respectively. The efficacy of MVA was noninferior to HVA in ITT analysis (difference: -1.6%, 97.5% CI: -7.0% to 3.8%, p < 0.001) and PP analysis (difference: -1.7%, 97.5% CI: -7.1% to 3.7%, p < 0.001); LVA's effectiveness was less than HVA in ITT analysis (difference: -6.2%, 97.5% CI: -12.2% to -0.2%, p = 0.076) and PP analysis (difference:-6.4%, 97.5% CI: -12.4% to -0.3%, p = 0.089). The incidence of AEs and medication compliance among the three groups was similar.

Conclusions: A 14-day VA regimen requires ≥ 2 g/d amoxicillin to maintain noninferior eradication efficacy versus 3 g/d, supporting dose reduction without compromising effectiveness.

Trial registration: ClinicalTrials.gov identifier: NCT05649540.

Keywords: Helicobacter pylori; amoxicillin; dual therapy; noninferiority; vonoprazan.

Publication types

  • Clinical Trial, Phase IV
  • Equivalence Trial
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amoxicillin* / administration & dosage
  • Anti-Bacterial Agents* / administration & dosage
  • China
  • Drug Therapy, Combination
  • Female
  • Helicobacter Infections* / drug therapy
  • Helicobacter Infections* / microbiology
  • Helicobacter pylori* / drug effects
  • Humans
  • Male
  • Middle Aged
  • Proton Pump Inhibitors* / administration & dosage
  • Pyrroles* / administration & dosage
  • Sulfonamides* / administration & dosage
  • Treatment Outcome

Substances

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

Associated data

  • ClinicalTrials.gov/NCT05649540