Vonoprazan Dual or Triple Therapy Versus Bismuth‐Quadruple Therapy as First‐Line Therapy for Helicobacter pylori Infection: A Three‐Arm, Randomized Clinical Trial

ABSTRACT Background We compared efficacy of vonoprazan‐dual or triple therapies and bismuth‐quadruple therapy for treatment‐naive Helicobacter pylori (HP) infection in Southern China, where primary resistance rates of clarithromycin and levofloxacin are >30%. Methods This was an investigator‐initiated, three‐arm, randomized clinical trial in Southern China. Between March 2022 and August 2023, treatment‐naïve HP‐infected adults were randomly assigned to receive one of three 14‐day regimens (1:1:1 ratio): vonoprazan‐dual (VA‐dual; vonoprazan 20 mg twice daily and amoxicillin 1 g thrice daily), vonoprazan‐triple (VAC‐triple; vonoprazan 20 mg/amoxicillin 1 g/clarithromycin 500 mg twice daily), or bismuth‐quadruple therapy containing bismuth, esomeprazole, tetracycline, and metronidazole. Primary outcome was noninferiority in HP eradication, evaluated by UBT 4–6 weeks post‐treatment by intention‐to‐treat (ITT) and per‐protocol (PP) analysis (based on subjects who completed 14‐day treatment and rechecked UBT). Bonferroni‐adjusted p‐value of