Potassium-Competitive Acid Blocker–Based Triple Therapy versus Proton Pump Inhibitor–Based Triple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Abstract

Introduction: Gastric acid secretion is strongly and persistently inhibited by potassium competitive acid blocker (P-CAB). The safety and effectiveness of P-CAB-based triple therapy versus conventional proton pump inhibitor (PPI)-based triple therapy for eradication of Helicobacter pylori have been examined in a number of studies, however the outcomes are still inconsistent. To assess the safety, treatment compliance/adherence, and effectiveness of P-CAB-based triple therapy in comparison to PPIbased triple therapy for the eradication of H. pylori, we have conducted this systematic review and meta-analysis.

Methods: The PRISMA 2020 requirements for systematic review and meta-analysis were adhered to. Randomized controlled trials (RCTs) comparing P-CAB-based triple therapy with PPI-based triple therapy (PTT) for H. pylori eradication that were published between February 2015 and February 2026 were found by searching MEDLINE, Embase, and the Cochrane Library. Informations were gathered on treatment compliance/adherence, adverse drug reactions, and the eradication rates (intentionto-treat analysis). Pooled risk ratios (RR) at 95% confidence intervals (CI) were computed using Review Manager.

Results: The analysis includes eight randomized controlled trials (RCTs) with 2378 individuals. Six RCTs evaluated vonoprazanbased triple therapy (VTT), while two RCTs assessed tegoprazan-based triple therapy (TTT). Pooled analysis of six RCTs (1780 patients) evaluating VTT showed significantly higher eradication rate compared with PTT (806/898 vs 695/882; RR:1.13, 95% CI 1.04–1.23; P = 0.004), although substantial heterogeneity was observed (I² = 75%, Chi² = 19.50, P = 0.002). TTT was found to be non-inferior to PTT in two studies with 598 participants (214/296 vs. 206/302; RR:1.07; 95% CI 0.98–1.18; P = 0.14) with no heterogeneity (I² = 0%, Chi² = 0.24, P = 0.62). In both intervention and control groups across all RCTs, treatment compliance was at least 90%. The common encountered adverse drug reactions by the participants of either group were nausea, diarrhea, abdominal discomfort, headache, and altered taste. These reactions were generally minor and similar in the intervention and control groups.

Conclusion: P-CAB-based triple therapy appears to be an effective and well-tolerated alternative to conventional PPI-based therapy. Although VTT showed better eradication rates than PTT, TTT exhibited non-inferior efficacy. Before validating these results, further large-scale, multi-center, and multi-national trials across diverse populations are required.