Background: Bismuth quadruple therapy is currently the recommended first-line regimen for Helicobacter pylori (H. pylori) infection in regions with high clarithromycin resistance. Recent randomized trials showed that 7-day vonoprazan-based triple therapy is superior to 7-day lansoprazole-based triple therapy in Japanese. A recent trial further showed that 7-day vonoprazan-based high dose amoxicillin dual therapy was non-inferior to 7-day vonoprazan-based triple therapy in Japanese. However, whether vonoprazan based dual, triple, and quadruple therapies are superior or non-inferior to lansoprazole based triple or quadruple therapy remains unknown.
Objective: The investigators aimed to compare the efficacy and safety of 14-day vonoprazan-based dual therapy, triple therapy, bismuth quadruple therapy, reverse hybrid therapy, and lansoprazole-based bismuth quadruple therapy and triple therapy in the first-line treatment of H. pylori infection in this pilot study.
Methods: Using a block randomization with a block size of 16 in a 1:1 ratio, 1200 eligible adult subjects aged 20 years or greater with at least two positive tests for H. pylori infection will be randomized to receive one of the following regimens: (A) vonoprazan-based triple therapy for 14 days (T-V14): vonoprazan 20mg twice daily, clarithromycin-XL 500mg twice daily, amoxicillin 1000mg twice daily for 14 days ; or (B) vonoprazan-based triple therapy for 7 days (T-V7): vonoprazan 20mg twice daily, clarithromycin-XL 500mg twice daily, amoxicillin 1000mg twice daily for 7 days ; or (C): vonoprazan-based dual therapy for 14 days (D-V14): vonoprazan 20mg twice daily, amoxicillin 750mg every 8 hour for 14 days; (D): vonoprazan-based high dose dual therapy for 14 days (HD-V14): vonoprazan 20mg twice daily, amoxicillin 750mg four times a day for 14 days; or (E) vonoprazan-based bismuth quadruple therapy for 14 days (BQ-V14) vonoprazan 20mg twice daily, bismuth tripotassium dicitrate 300 mg three times a day, tetracycline 500mg three times a day, and metronidazole 500mg three times a day for 14 days; or (F) vonoprazan-based reverse hybrid therapy for 14 days (RH-V14): vonoprazan 20mg twice daily, and amoxicillin 1000mg twice daily for 14 days, plus clarithromycin-XL 500mg twice daily and metronidazole 500mg twice daily for the first 7 days ; or (G) lansoprazole-based bismuth quadruple therapy for 14 days (BQ-L14) lansoprazole 30mg twice daily, bismuth tripotassium dicitrate 300 mg three times a day, tetracycline 500mg three times a day, and metronidazole 500mg three times a day for 14 days; or (H) lansoprazole-based triple therapy for 14 days (T-L14): lansoprazole 30mg twice daily, clarithromycin-XL 500mg twice daily, amoxicillin 1000mg twice daily for 14 days. Subjects who fail after first-line therapy will be randomized to receive either vonoprazan-based levofloxacin triple therapy (LT-V14) containing vonoprazan 20mg twice daily, levofloxacin 250mg twice daily, and amoxicillin 1000mg twice daily for 14 days or vonoprazan-based levofloxacin reverse hybrid therapy (LRH-V14) containing vonoprazan 20mg twice daily, and amoxicillin 1000mg twice daily for 14 days, plus levofloxacin 250mg twice daily and metronidazole 500mg twice daily for the first 7 days. The minimum inhibitory concentrations will be determined by agar dilution test. 23S ribosomal RNA and gyrase A mutations will be determined by PCR methods followed by direct sequencing in a subgroup of patients. The TWB2.0 SNP array will be used for genotyping of genome wide single nucleotide polymorphism.
Outcome analysis: The primary outcome is the eradication rate in the first-line treatment. The secondary outcomes are the compliance, frequency of adverse events, the overall eradication rate after two treatments.