Efficacy of Vonoprazan-Doxycycline Dual Therapy for the Treatment of Helicobacter pylori Infection: A Retrospective Cohort Study

Objective: To compare the efficacy and safety of vonoprazan-doxycycline dual therapy versus vonoprazan-amoxicillin high-dose dual therapy as first-line eradication treatment for Helicobacter pylori (H. pylori) infection. Methods: This retrospective study collected clinical data from 357 patients with confirmed H. pylori infection who received first-line eradication therapy at the People’s Hospital of Ningxia Hui Autonomous Region, The Third People’s Hospital of Shizuishan City, and Yanchi County People’s Hospital between December 2024 and December 2025. Patients aged 18– 80 years with active H. pylori infection confirmed by 1 3 C/ 1 4 C urea breath test or histopathology were included. Key exclusion criteria included allergy to study medications, severe organ dysfunction, pregnancy, and incomplete medical records. Based on the treatment regimen, patients were divided into a vonoprazan-doxycycline dual-therapy group (doxycycline group, n = 180) and a vonoprazan-amoxicillin high-dose dual-therapy group (amoxicillin group, n = 177). Eradication outcomes were assessed by 1 3 C/ 1 4 C urea breath test four weeks after treatment completion. Adverse events were recorded during follow-up. Results: ITT eradication rates were 76.1% (137/180) in the doxycycline group and 78.0% (138/177) in the amoxicillin group, with both falling below the commonly accepted 80% threshold for first-line therapy; PP eradication rates were 87.3% (137/157) and 89.0% (138/155), respectively. No statistically significant differences were observed in either analysis (both P > 0.05). At least one adverse event occurred in 31 patients (19.7%) in the doxycycline group versus 17 patients (11.0%) in the amoxicillin group, with a statistically significant difference in overall adverse event rates ( P ≤ 0.05). The incidence of nausea/vomiting and decreased appetite was significantly higher in the doxycycline group (both P ≤ 0.05), whereas no significant differences were observed for other adverse events (all P > 0.05). All adverse events were mild to moderate; no patient discontinued treatment, and all symptoms resolved or improved after therapy completion. Conclusion: Vonoprazan-doxycycline dual therapy may achieve comparable eradication efficacy to vonoprazan-amoxicillin dual therapy for H. pylori . Although the overall incidence of adverse events was higher in the doxycycline group, all were mild to moderate and well tolerated. This regimen may serve as a potential treatment alternative for patients with penicillin allergy or those requiring simplified treatment regimens, pending confirmation by prospective multicenter randomized trials. Keywords: Helicobacter pylori , vonoprazan, doxycycline, amoxicillin, eradication rate, adverse events, retrospective study