Clinical impact of high-dose esomeprazole-amoxicillin dual therapy as rescue treatment for Helicobacter pylori infection: a meta-analysis of randomized controlled trials

BACKGROUND: Helicobacter pylori infection, linked to peptic ulcer disease and gastric cancer, faces declining eradication rates due to antibiotic resistance. High-dose esomeprazole-amoxicillin dual therapy (HDDT) is a promising rescue regimen, but its efficacy and safety compared to standard therapies remain unclear. METHODS: This systematic review and meta-analysis, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, included four randomized controlled trials (n = 1,230) that compared HDDT with standard regimens. PubMed, Embase, and Cochrane CENTRAL were searched through April 2025. Outcomes included eradication rates, compliance, and adverse events. A meta-analysis was conducted using the inverse variance method, with heterogeneity assessed via I² statistics. RESULTS: HDDT showed no significant difference in eradication rates (RR = 0.98, 95% CI: 0.89-1.08, P = 0.6438) or compliance (RR = 1.04, 95% CI: 0.97 to 1.12, P = 0.2522) compared to standard therapies. However, HDDT significantly reduced overall adverse events (RR = 0.28, 95% CI: 0.18-0.44, P < 0.0001), including nausea, headache, fatigue, dysgeusia, bloating, and abdominal pain. No significant differences were observed for serious adverse events, diarrhea, dizziness, decreased appetite, constipation, or skin rash. Heterogeneity varied across the outcomes. CONCLUSION: HDDT is as effective as standard regimens for H. pylori rescue treatment, with a superior safety profile, supporting its use in patients with prior treatment failures.