Abstract

INTRODUCTION: In Chile, Helicobacter pylori infection remains highly prevalent, with clarithromycin resistance exceeding 26%, limiting the effectiveness of standard triple therapy (63.8% eradication). Prior data suggest that optimized acid suppression is critical: a dual regimen using high-dose amoxicillin and esomeprazole achieved 91.8% eradication. Fexuprazan, a potassium-competitive acid blocker (PCAB) with faster and stronger acid inhibition than PPIs, has not yet been evaluated in this setting. AIM: (1) To compare the intentionto-treat (ITT) and per-protocol (PP) effectiveness of high-dose dual therapy with amoxicillin plus esomeprazole versus amoxicillin plus fexuprazan; (2) to compare adverse events between regimens; and (3) to assess cost-effectiveness using incremental cost-effectiveness ratios (ICER). METHODS: Patients with a positive rapid urease test obtained during upper endoscopy were included. Individuals with prior eradication attempts were excluded. One group received esomeprazole 40 mg three times daily plus amoxicillin 750 mg four times daily; the other received fexuprazan 40 mg twice daily with the same amoxicillin regimen. Treatment duration was 14 days. Eradication was assessed 6 weeks post-therapy using stool H. pylori antigen testing; a negative result confirmed eradication. Groups were blinded-matched 1:1 by sex, age, BMI, and other variables. Statistical analyses were performed with Prism 9.0 using Mann–Whitney and chi-square tests. Cost effectiveness analyses were performed using ICER. RESULTS: A total of 130 patients were included (65 per group). Eradication rates were 92.3% with fexuprazan-based dual therapy and 89.2% with esomeprazole-based therapy (p=0.051). Adverse events were less frequent with fexuprazan (4.6% vs. 9.2%, p=0.04), and no severe adverse events occurred in the fexuprazan group (0% vs. 4.3%, p=0.001) (Figure 1). Cost-effectiveness analysis yielded an ICER of 699.3, favoring esomeprazole due to lower upfront cost, although this did not account for additional costs of second-line therapy—where fexuprazan becomes more cost-effective given its higher eradication rate. CONCLUSIONS: Preliminary data suggest that high-dose dual therapy with fexuprazan is at least as effective as esomeprazole-based dual therapy and is associated with fewer adverse events. Ongoing studies with larger sample sizes will help determine whether high-dose fexuprazan plus amoxicillin may represent a superior first-line strategy for H. pylori eradication.