Efficacy and Safety of Vonoprazan‐Based Dual, Triple, and Quadruple Therapies for Helicobacter pylori Eradication: A Randomized Controlled Trial

BACKGROUND: Vonoprazan (VPZ), a potassium-competitive acid blocker, has shown promising efficacy in Helicobacter pylori (H. pylori) eradication. However, direct comparisons of VPZ-based dual therapy (V-DT), triple therapy (V-TT), and bismuth quadruple therapy (V-BQT) remain limited. This study aimed to evaluate and compare the efficacy, safety, and compliance of these three regimens as first-line treatments for H. pylori infection. METHODS: 375 adults were randomized (1:1:1) to receive V-DT (VPZ 20 mg bid + amoxicillin 1 g tid for 10 days), V-TT (VPZ 20 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid for 14 days), or V-BQT (VPZ 20 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid + bismuth 240 mg bid for 10 days). The primary outcome was H. pylori eradication rate by intention-to-treat (ITT), modified ITT (mITT), and per-protocol (PP) analyses. Secondary outcomes included adverse events and compliance. RESULTS: Eradication rates were 92.0% (95% confidence interval [CI]: 85.8%-96.1%), 89.6% (95% CI: 82.9%-94.3%), and 88.8% (95% CI: 81.9%-93.7%) in ITT; 94.3% (95% CI: 88.5%-97.7%), 94.9% (95% CI: 89.3%-98.1%), and 94.1% (95% CI: 88.2%-97.6%) in mITT; and 94.2% (95% CI: 88.4%-97.6%), 95.6% (95% CI: 90.0%-98.5%), and 94.8% (95% CI: 89.0%-98.1%) in PP analyses for V-DT, V-TT, and V-BQT, respectively. The efficacy of V-DT and V-TT was noninferior to that of V-BQT. Adverse events were significantly lower with V-DT (6.4%) than with V-TT (36.0%) and V-BQT (49.6%) (p < 0.001). Compliance exceeded 93% in all groups, with no significant differences (p = 0.250). CONCLUSIONS: All three regimens achieved high eradication rates, with V-DT and V-TT being statistically noninferior to V-BQT. The 10-day V-DT regimen achieved eradication rates comparable to V-BQT with substantially fewer adverse events and reduced antibiotic use, supporting its potential as a simplified first-line option for H. pylori eradication. TRIAL REGISTRATION: Chinese Clinical Trial Registration Number: ChiCTR2300072857.