14-Day High-Dose Amoxicillin- and Metronidazole-Containing Triple Therapy With or Without Bismuth as First-Line Helicobacter pylori Treatment.

BACKGROUND: Amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy had been shown to reliably achieve high eradication rates. The role of individual components remains undefined. AIM: To identify the additional benefit/role of bismuth in amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. METHODS: This was a non-inferiority factorial design trial. Treatment-naive H. pylori-infected subjects were randomly (1:1) assigned to receive 14-day amoxicillin- and metronidazole-containing triple therapy consisting of esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg both thrice daily with or without 220 mg bismuth twice a day. Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. RESULTS: From July 2018 to June 2019, a total of two hundred and sixteen subjects were randomized. Both therapies achieved high eradication rates. Per-protocol with bismuth = 97.9% (94/96, 95% CI 95.1-100%) and without bismuth = 94.7% (90/95, 95% CI 90.3-99.1%) (P = 0.43). Intent-to-treat analysis = 90.7% (98/108, 95% CI 85.2-96.2%) versus 88.9% (96/108, 95% CI 82.8-95.0%) with and without bismuth (P = 0.65). The two regimens were not inferior by intent-to-treat or per-protocol analyses. Metronidazole resistance did not affect the efficacy of either therapy. CONCLUSION: Neither the presence nor absence of bismuth or metronidazole resistance reduced the effectiveness of triple therapy containing esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg thrice daily in this population. The clinical trial was registered with ClinicalTrials.gov, NCT03557437.