High-Dose Dual Therapy Versus Bismuth Quadruple Therapy for Rescue Treatment of Helicobacter pylori: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Background/Aims: Failure of first-line Helicobacter pylori (HP) eradication therapy occurs in approximately 3%-24% of patients. Highdose dual therapy (HDDT) has been proposed as an alternative rescue regimen. This meta analysis compared the efficacy and safety of HDDT and bismuth-containing quadruple therapy (BQT) in patients undergoing rescue eradication therapy.

Materials and Methods: Randomized controlled trials (RCTs) comparing HDDT with BQT for HP rescue therapy were systematically searched in multiple databases from January 1, 2000, to June 30, 2025. Primary outcomes were eradication rates based on intention-totreat (ITT) and per-protocol (PP) analyses. Secondary outcomes included treatment compliance and adverse events. Statistical analyses were performed using Stata 18.0 and RevMan 5.4.

Results: Ten RCTs involving 2458 patients were included. In the ITT analysis, HP eradication rates were comparable between the HDDT and BQT groups (81.09% vs. 80.02%, relative risk (RR) = 1.01, 95% CI: 0.97-1.05, P = .54). Similarly, no significant difference was observed in the PP analysis (86.42% vs. 86.27%, RR = 1.00, 95% CI: 0.97-1.03, P = .90). However, HDDT was associated with significantly lower incidence of adverse events (14.00% vs. 35.13%, RR = 0.40, 95% CI: 0.31-0.51, P < .00001) and higher patient compliance (92.75% vs. 88.62%, RR = 1.08, 95% CI: 1.01-1.14, P = .02) compared with BQT.

Conclusion: HDDT achieved eradication rates comparable to those of BQT for rescue therapy after initial treatment failure, with fewer adverse events and better patient compliance.

Cite this article as: Lin N, Liu J, Yang C. High-dose dual therapy versus bismuth quadruple therapy for rescue treatment of Helicobacter pylori: A systematic review and meta-analysis of randomized controlled trials. Turk J Gastroenterol. 2026;37(6):702-713.