Vonoprazan versus rabeprazole in dual therapy with amoxicillin for Helicobacter pylori eradication: a prospective, multicenter, open-label, randomized controlled trial

Both traditional proton pump inhibitors and the novel potassium-competitive acid blocker vonoprazan, when combined with high-dose amoxicillin in dual therapy, have shown promise for Helicobacter pylori (H. pylori) eradication. However, high-quality evidence directly comparing their efficacy and safety remains limited. This study aimed to compare the clinical efficacy and safety of rabeprazole-amoxicillin dual therapy versus vonoprazan-amoxicillin dual therapy for H. pylori eradication. From April 1, 2024, to February 28, 2025, 318 H. pylori-positive patients were enrolled and randomly assigned in a 1:1 ratio to two treatment groups: the Rabeprazole Group (rabeprazole 20 mg twice daily; amoxicillin 1000 mg three times daily) and the Vonoprazan Group (vonoprazan 20 mg twice daily; amoxicillin 1000 mg three times daily). Both groups received a 14-day treatment course. A 13C-urea breath test was performed at least four weeks after treatment completion. H. pylori eradication rates, incidence of adverse events during treatment, and medication adherence were compared between the groups. In the intention-to-treat analysis, the eradication rates were 75.5% (95% CI: 68.8%-82.2%) in the Rabeprazole Group and 83.0% (95% CI: 77.2%-88.9%) in the Vonoprazan Group, with no statistically significant difference (P = 0.097). In the modified intention-to-treat analysis, the rates were 78.4% (95% CI: 71.9%-84.9%) and 88.6% (95% CI: 83.5%-93.7%), respectively, showing a significant difference (P = 0.018). In the per-protocol analysis, the rates were 79.7% (95% CI: 73.1%-86.3%) and 90.1% (95% CI: 85.1%-95.0%), respectively, also showing a significant difference (P = 0.015). The incidence of adverse events was low in both groups (10.5% vs. 12.8%, P = 0.533). Medication adherence did not differ significantly between the groups (P = 0.648). Manual labor occupation was identified as a risk factor for eradication failure (adjusted OR = 2.153, 95% CI: 1.067 to 4.346, P = 0.032). Vonoprazan-amoxicillin dual therapy achieves satisfactory outcomes for H. pylori eradication, with a significantly higher eradication rate than the traditional rabeprazole-amoxicillin dual regimen. As a novel acid suppressant, vonoprazan demonstrates significant clinical advantages and broad application potential in dual-therapy regimens for H. pylori eradication. https://www.medicalresearch.org.cn/, identifier ChiCTR2400082319. Registered on March 5, 2024.