Vonoprazan improves the efficacy of bismuth quadruple therapy containing doxycycline and metronidazole as first-line Helicobacter pylori treatment in penicillin-allergic patients: a randomized controlled trial

Abstract Background Helicobacter pylori eradication in penicillin-allergic patients presents challenges. Options of effective regimens are lacking in areas where tetracycline is unavailable. Objectives To evaluate the efficacy of replacing the proton pump inhibitor (PPI) with a potassium-competitive acid blocker (P-CAB, vonoprazan) in standard bismuth quadruple therapy containing doxycycline and metronidazole as a first-line treatment for H. pylori. Methods This prospective randomized clinical trial enrolled 332 naive patients with H. pylori infection and penicillin allergy. Participants were randomly assigned in a 1:1 ratio to either the 14 day P-CAB/BDM group (vonoprazan 20 mg twice daily, colloidal bismuth 200 mg twice daily, doxycycline 100 mg twice daily and metronidazole 400 mg three times daily) or the 14 day PPI/BDM group (rabeprazole 10 mg twice daily, and the same dose of the three other drugs as in the 14 day P-CAB/BDM group). Results Eradication rates in the P-CAB/BDM and PPI/BDM groups were 90.4% and 71.1% (P value for superiority was 0.013), respectively, by ITT analysis. The efficacy of P-CAB/BDM remained non-inferior and even superior to PPI/BDM therapy in all ITT, modified ITT and PP analyses. The overall frequency of adverse events (39.8% and 40.4%; P = 0.911) and compliance (88.0% and 91.0%; P = 0.372) were similar between P-CAB and PPI regimens. Patients with higher body surface area were significantly associated with eradication failure in both groups (P < 0.05). Conclusions The 14 day P-CAB/BDM therapy provided a satisfactory eradication rate of >90% (ITT analysis) and had a good safety profile as first-line H. pylori therapy, providing an alternative option for penicillin-allergic patients.