Efficacy and Safety of Vonoprazan-Based Dual Therapies With Different Antibiotics Versus Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Prospective, Four-Arm, Randomized Controlled Trial.

Abstract

Vonoprazan-based dual therapy has been proposed as a simplified strategy for Helicobacter pylori eradication, but head-to-head comparisons of different antibiotic partners are limited. We compared the efficacy, safety, and adherence of vonoprazan-based dual regimens with those of bismuth-containing quadruple therapy (BQT). In this randomized controlled trial, H. pylori-infected patients were allocated (1:1:1:1) to receive VA (vonoprazan [20 mg, bid] plus amoxicillin [1000 mg, tid]), VT (vonoprazan [20 mg, bid] plus tetracycline [500 mg, tid]), VM (vonoprazan [20 mg, bid] plus minocycline [100 mg, bid]), or VACB (vonoprazan [20 mg, bid], amoxicillin [1000 mg, bid], clarithromycin [500 mg, bid], and bismuth [220 mg, bid]) for 14 days. The primary endpoint was the H. pylori eradication rate, and the secondary endpoints were the incidence of adverse events and patient adherence. The ITT eradication rates were 83.0% (83/100), 74.0% (74/100), 82.0% (82/100), and 83.0% (83/100) in the VA, VT, VM, and VACB groups, respectively (p = 0.304). The PP eradication rates were 90.2% (83/92), 83.1% (74/89), 88.2% (82/93), and 92.2% (83/90), respectively (p = 0.262). Adverse events occurred in 21.5% of the patients overall and differed across groups (10.0%, 15.0%, 29.0%, and 32.0% in VA, VT, VM, and VACB, respectively; p < 0.001); nausea and dizziness were more frequent with VM, whereas bitter taste and black stool were more frequent with VACB. All adverse events were mild or moderate, and no severe events were recorded. Adherence was high and comparable across groups (VA 100.0%, VT 96.0%, VM 99.0%, VACB 99.0%; p = 0.107). Vonoprazan-based regimens showed no statistically significant between-group differences in eradication and were associated with good adherence overall. In our setting, VA and VM may represent practical simplified options, whereas VT appeared less robust as an empiric regimen. These exploratory findings warrant confirmation in larger, adequately powered randomized trials. ClinicalTrials.gov (NCT07068607).