Fourteen-day vonoprazan-based dual therapy with amoxicillin as first-line Helicobacter pylori treatment in comparison with sequential therapy: A randomized controlled trial

BACKGROUND AND AIM: Proton pump inhibitor-based therapies remain the mainstream standard for Helicobacter pylori (H. pylori) eradication because of their lower cost and accessibility. Among these, 14-day sequential therapy (S-14) is a widely established and effective regimen with a relatively lower pill burden. Recently, 14-day vonoprazan-amoxicillin dual therapy (VA-14) has emerged as a promising alternative with similar therapeutic advantages. This study compared the efficacy and safety of VA-14 versus S-14 as first-line therapy. METHODS: This single-center, prospective, randomized, non-inferiority trial enrolled 337 treatment-naïve adults. Participants were assigned to VA-14 (vonoprazan 20 mg plus amoxicillin 1000 mg twice daily for 14 days) or S-14 (lansoprazole 30 mg plus amoxicillin 1000 mg twice daily for 7 days, followed by lansoprazole 30 mg, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 7 days). The primary endpoint was eradication rate assessed by urea breath test. Secondary outcomes included adverse events (AEs) and adherence. RESULTS: Intention-to-treat eradication rates were 83.9% with VA-14 and 74.0% with S-14. Per-protocol rates were 90.9% and 85.6%, respectively, demonstrating non-inferiority (P < 0.001). AEs were significantly less frequent with VA-14 (42.8% vs 78.3%, P < 0.01), including severe AEs (4.2% vs 14.3%, P < 0.01). Full adherence was higher with VA-14 (93.8% vs 90.0%, P = 0.04). CONCLUSIONS: Fourteen-day vonoprazan-amoxicillin dual therapy is non-inferior to sequential therapy for first-line H. pylori eradication and offers better tolerability and adherence, representing a simplified and viable low pill burden option. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT06156085.