Comparative Efficacy and Safety of Vonoprazan–Amoxicillin Dual Therapy Versus Clarithromycin-Based Standard Triple Therapy for Helicobacter pylori Eradication: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Introduction: The declining efficacy of standard triple therapy for Helicobacter pylori (H. pylori) eradication, largely driven by increasing antibiotic resistance, has highlighted the need for alternative treatment strategies. Vonoprazan–amoxicillin dual therapy (VDT) has emerged as a promising regimen due to the potent and sustained acid suppression provided by vonoprazan. This meta-analysis aims to compare the efficacy and safety of VDT versus clarithromycin-based standard triple therapy (STT) for H. pylori eradication in adults. Methods: A systematic search of PubMed, Scopus, and the Cochrane Library was conducted from inception to 15 March 2026 for randomized controlled trials (RCTs) comparing VDT (vonoprazan plus amoxicillin) with STT (proton pump inhibitor, amoxicillin, and clarithromycin) for H. pylori eradication (PROSPERO “CRD420261357715”). Heterogeneity was assessed using the I2 statistic and Cochran’s Q test. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using the Mantel–Haenszel method within a restricted maximum-likelihood random-effects model. Results: Five RCTs were included with 1363 patients (VDT: 680, STT: 683). VDT demonstrated a significantly higher H. pylori eradication rate compared with STT (RR 1.17; 95% CI [1.07; 1.27]; p = 0.007; I2 = 11%). Conclusions: This meta-analysis suggests that VDT may be associated with higher H. pylori eradication rates than clarithromycin-based STT. Further large, well-designed RCTs are needed before firm first-line recommendations can be made.