Abstract Background To date, no interventional trial has assessed the efficacy and safety of vonoprazan and high‐dose (500 mg four times daily, 2000 mg/day) amoxicillin dual therapy in terms of Helicobacter pylori eradication. We explored whether this was an appropriate first‐line treatment. Methods This prospective, dual‐center, single‐arm interventional study was performed in Japan. Twenty H. pylori‐positive patients lacking any eradication history were treated with vonoprazan 20 mg twice daily and amoxicillin 500 mg four times daily (qid) for 7 days. Eradication was evaluated using a stool H. pylori antigen test. We evaluated safety using patient questionnaires. This study was registered in the jRCT database (jRCT031200128). Results The intention‐to‐treat and per‐protocol eradication rates were 90% (95% confidence interval [CI] 68.3–98.8%, n = 20) and 94.4% (95% CI 72.7–99.9%, n = 18) respectively. No significant adverse event was recorded. Conclusion Vonoprazan/high‐dose amoxicillin dual therapy can be a safe standard first‐line therapy. We are now undergoing a randomized controlled trial comparing dual therapy and vonoprazan‐based triple therapy.
