High-Dose Dual Therapy Versus Bismuth-Containing Quadruple Therapy as Rescue Treatment for Helicobacter pylori Infection: Systematic Review and Meta-Analysis.

Abstract

Bismuth-containing quadruple therapy (BQT) is recommended for H. pylori rescue treatment, but many patients cope with pill burden and adverse events. High-dose dual therapy (HDDT) may be easier to tolerate. We compared HDDT with BQT in rescue therapy. We followed PRISMA 2020 (PROSPERO CRD420251266898) and searched PubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science Core Collection, CiNii Research, and Major Chinese Databases (CNKI, Wanfang Data, and VIP) through December 16, 2025. We pooled head-to-head rescue RCTs comparing HDDT (PPI/PCAB + Amoxicillin ≥ 3 g/Day, ≥ TID) with BQT using random-effects models. risk of bias was assessed with RoB 2 and certainty with GRADE. TSA assessed information size for the primary ITT outcome. Ten RCTs (n = 2407) showed comparable ITT eradication for HDDT vs. BQT (79.9% vs. 79.9%, RR 1.01, 95% CI 0.97-1.05; I² = 3.9%). Any adverse events were less frequent with HDDT (122/1135, 10.7%) than BQT (334/1123, 29.7%). The corresponding meta-analysis (expressed as AE-free so that RR > 1 favors HDDT) showed RR 1.27, 95% CI 1.15-1.41. TSA suggested that the required information size for the primary ITT outcome was reached, making a clinically important (≥ 10%) relative difference in ITT eradication unlikely. In rescue patients without penicillin allergy, HDDT achieves eradication comparable to BQT while causing far fewer adverse events. HDDT is a practical rescue option when BQT is poorly tolerated, although most evidence comes from China and reporting of adherence and resistance is uneven.