High-dose dual therapy bismuth-containing quadruple therapy for eradication: a systematic review and meta-analysis with trial sequential analysis

Background and objective: Recently, a large number of trials on proton pump inhibitor-amoxicillin-containing high-dose dual therapy (HDDT) versus bismuth-containing quadruple therapy (BQT) for Helicobacter pylori ( H. pylori ) eradication have been published with controversial and inconsistent conclusions. The aim of this meta-analysis was to determine the effects of HDDT for H. pylori eradication compared to BQT. Design: A systematic review and meta-analysis was conducted. Methods: PubMed, Embase, and the Cochrane library database were searched to collect all randomized controlled trials (RCTs) assessing the effects of HDDT versus BQT to H. pylori eradication from inception to September 2022. Meta-analysis was conducted to estimate the pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effects model. Quality of evidence was appraised using Grading of Recommendations, Assessment, Development and Evaluation system. Trial sequential analysis (TSA) was performed to determine the reliability and conclusiveness. Results: A total of 14 RCTs with 5121 patients were included. The results of meta-analysis showed that there was no statistical significance in the eradication rate between HDDT and BQT (intention-to-treat analysis: 86.7% versus 85.1%, RR = 1.01, 95% CI: 0.98–1.04; per-protocol analysis: 89.9% versus 89.4%, RR = 1.01, 95% CI: 0.98–1.03; moderate-quality evidence). The incidence of total adverse effects in HDDT group was significantly lower than in BQT group (5.9% versus 34.1%, RR = 0.42, 95% CI: 0.34–0.50; low-quality evidence). No statistical significance was observed in compliance between HDDT and BQT (RR = 1.01, 95% CI, 1.00–1.03, p = 0.07; low-quality evidence). The TSA result for H. pylori eradication rate indicated that the effect was conclusive. Conclusions: Evidence from our updated meta-analysis suggests that HDDT is as effective as BQT in eradicating H. pylori , with fewer adverse effects and similar compliance. Registration: Open Science Framework registries (No: osf.io/th4vd)