ABSTRACT Objectives 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. Materials and Methods 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. Results 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; I 2 = 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. Conclusions 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.
Zhang et al. (2026) studied this question.