Background/Aims: Although a potassium-competitive acid blocker (PCAB)-based regimen improves the rate of successful Helicobacter pylori first-line eradication, the efficacy of a PCAB-based regimen as second-line therapy is unclear. The aim of this study is to compare the success of second-line eradication of H. pylori using PCAB and proton pump inhibitor (PPI)-based regimens. Methods: From 2014 to 2017, 624 patients who underwent second-line H. pylori eradication were enrolled. A standard triple regimen for second-line H. pylori eradication includes metronidazole 250 mg, amoxicillin 750 mg, and PPI or PCAB twice daily for 7 days. The success of eradication was compared using intention-to-treat, per-protocol, and propensity-score matching analysis. Results: All patients completed the 7-day course of therapy. Patients using a PCAB-based regimen had a higher rate of eradication than those using a PPI-based regimen in both intention-to-treat (90% [298/330] vs. 85% [250/294], p = 0.045) and per-protocol analyses (96% [298/309] vs. 91% [250/274], p = 0.008). Adverse events occurred in 4 patients. Propensity score matching analysis acquired 274 matched pairs. Patients using a PCAB-based regimen had a higher rate of eradication than those using a PPI-based regimen (96% [264/274] vs. 91% [250/274], p = 0.013). Conclusions: PCAB-based second-line H. pylori eradication is significantly better than PPI-based therapy.

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