Real-World effectiveness of high-dose dual therapy vs optimized clarithromycin triple therapy for Helicobacter Pylori: a prospective cohort study with test-of-cure sensitivity analyses

Ugarte Lastra A.; Advincula Solis D.E.; Ramos Mamani H.; Cedrón Cheng H.G.; Bellido-Caparo Á.; Montezuma Calvo D.; Vesco Monteagudo E.; Poppele Molina G.; Chirinos Vega J.A.; Espinoza-Ríos J.; Frías-Ordoñez J.S.; Aguilar Sánchez V.; Pinto Valdivia J.L.; Huerta Mercado Tenorio J. · Arquivos de Gastroenterologia (2026) · DOI: 10.1590/s0004-2803.24612026-014

Resumen

– Background – Helicobacter pylori eradication rates have declined globally due to rising antibiotic resistance, challenging the effectiveness of standard triple therapy. High-dose dual therapy has emerged as a simplified alternative supported by pharmacodynamic rationale. We aimed to compare the real-world effectiveness, adherence, and safety of high-dose dual therapy versus optimized clarithromycin-based triple therapy in routine gastroenterology practice. Methods – We conducted a prospective, multicenter observational cohort study in adult patients with confirmed H. pylori infection treated with either high-dose dual therapy (amoxicillin 1 g three times daily plus esomeprazole 40 mg three times daily for 14 days) or optimized clarithromycin-based triple therapy (amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, and esomeprazole 40 mg twice daily for 14 days) according to physician decision. Eradication was assessed by carbon-14 urea breath test ≥4 weeks after therapy. Comparative effectiveness was estimated with effect measures, 95% confidence intervals (CI), and predefined sensitivity analyses for incomplete test-of-cure follow-up. Results – Among 218 treated patients, 104 completed post-treatment breath testing. Eradication rates were 81.3% with high-dose dual therapy and 80.4% with triple therapy (absolute difference, +0.9%; 95%CI-14.9% to +16.7%; P=0.91). Moderate-to-high adherence was observed in 51.5% vs 67.6%, respectively (P=0.19). Adverse events were more frequent with high-dose dual therapy (70.8% vs 58.9%), although the difference was not statistically significant. Mainly gastrointestinal intolerance and taste disturbance. Sensitivity analyses across plausible missing-outcome scenarios showed stable comparative results. Conclusion – In prospective real-world practice, high-dose dual therapy achieved eradication effectiveness comparable to optimized triple therapy, with favorable tolerability. These findings support high-dose dual therapy as a pragmatic and clinically attractive alternative in settings with evolving resistance and adherence constraints.

Instituciones: Universidad Peruana Cayetano Heredia