Randomized trial of vonoprazan dual therapy vs bismuth-containing quadruple therapy with two low-resistance antibiotics for Helicobacter pylori eradication

Abstract

BACKGROUND

Given the escalating resistance rates to commonly used antibiotics in Helicobacter pylori (H. pylori) eradication, regimens containing two antibiotics with low resistance rates were increasingly used in clinical practice to maximize successful initial eradication.

AIM

To compare the efficacy and safety of vonoprazan-amoxicillin (VA) dual therapy and vonoprazan-based bismuth-containing quadruple therapy with two low-resistance antibiotics (amoxicillin and minocycline) in treatment-naïve H. pylori infection.

METHODS

A total of 184 treatment‐naïve H. pylori-infected patients were randomly assigned to receive either VA (vonoprazan fumarate 20 mg twice daily and amoxicillin 1000 mg three times daily) or VBAM (vonoprazan fumarate 20 mg twice daily, bismuth potassium citrate 240 mg twice daily, amoxicillin 1000 mg twice daily, and minocycline hydrochloride 100 mg twice daily) for 14 days. Adverse events and medication adherence were recorded during follow‐up. H. pylori eradication was assessed by a ¹³C- or ¹⁴C-urea breath test 4 weeks after treatment completion.

RESULTS

Eradication rates were 92.4% (85/92, 95%CI: 85.1%-96.3%) for VA and 91.3% (84/92, 95%CI: 83.8%-95.5%) for VBAM by intention‐to‐treat analysis (difference 1.1%; 95%CI: -6.8% to 9.0%; non-inferiority P = 0.003); 95.5% (85/89, 95%CI: 89.0%-98.2%) and 96.6% (84/87, 95%CI: 90.4%-98.8%) by modified intention‐to‐treat analysis (difference -1.1%; 95%CI: -6.8% to 4.7%; non-inferiority P = 0.001); 95.4% (83/87, 95%CI: 88.8%-98.2%) and 96.4% (81/84, 95%CI: 90.0%-98.8%) by per‐protocol analysis (difference -1.0%; 95%CI: -7.0% to 4.9%; non-inferiority P = 0.002). In all three analysis sets, the lower limits of the 95%CI for the rate difference were above the prespecified non-inferiority margin of -10%. No significant differences were observed between the two groups in overall adverse event incidence or adherence, but the incidence of dizziness was lower in the VA group (1.1% vs 9.8%, P = 0.023). The incremental cost-effectiveness ratio for VA vs VBAM was -15958.18 CNY per additional successfully eradicated patient from a healthcare payer perspective.

CONCLUSION

The VA dual regimen is non‐inferior to the VBAM quadruple therapy in eradication rate for treatment‐naïve H. pylori infection, while being associated with fewer dizziness events and lower direct medical costs from a healthcare payer perspective.

Keywords: Helicobacter pylori; Vonoprazan; Amoxicillin; Minocycline; Eradication; Safety; Randomized controlled trial

Core Tip: This single-center, open-label randomized trial compared vonoprazan-amoxicillin (VA) dual therapy with vonoprazan-based bismuth-containing quadruple therapy containing amoxicillin and minocycline (VBAM) in treatment-naïve Helicobacter pylori infection. VA was non-inferior to VBAM in eradication rates across all analysis sets. Overall adverse events were comparable, but VA had fewer dizziness events. From a healthcare payer perspective, VA had lower direct medical costs. However, the generalizability of these findings to broader populations and different resistance patterns requires further investigation.