Is Tailored Bismuth Quadruple Therapies (With Clarithromycin or Furazolidone) Based on Fecal Molecular Susceptibility Testing in First‐Line Helicobacter pylori Eradication Treatment More Effective? A Three‐Arm, Multicenter Randomized Clinical Trial

BACKGROUND: Rising antimicrobial resistance has significantly challenged the eradication rates of Helicobacter pylori. Due to its invasive nature, susceptibility testing based on endoscopic biopsy is controversial, while few studies have focused on the efficacy of tailored bismuth quadruple therapies (BQT) based on fecal susceptibility testing as a first-line treatment. METHODS: In this multicenter study, 598 H. pylori-positive patients without previous eradication treatment were recruited and randomly assigned to three groups: empirical BQT, BQT-tailored based on the history of clarithromycin use and tailored based on fecal molecular susceptibility testing where furazolidone was substituted for clarithromycin when there was clinical or laboratory evidence of clarithromycin resistance. This study defines BQT as regimens comprising rabeprazole, colloidal bismuth, amoxicillin, and one additional antibiotic (furazolidone or clarithromycin). The study assessed eradication rates using intention-to-treat (ITT), modified intention-to-treat (mITT), and per-protocol (PP) analyses. RESULTS: The eradication rates of three groups were 82.00%, 80.90%, and 87.44% in the ITT analysis; 82.41%, 83.42%, and 89.23% in the mITT analysis; and 85.86%, 87.50%, and 94.57% in the PP analysis, respectively. Tailored BQT based on fecal susceptibility testing was not inferior to empirical BQT (all p values for noninferiority < 0.001) and demonstrated greater efficacy in the PP analysis (difference [95% CI]: 7.07% [0.90%, 13.25%]). The incidence of adverse events and treatment compliance did not differ significantly among the groups. CONCLUSION: Tailored BQT based on fecal susceptibility testing is an effective regimen for H. pylori eradication, with no increase in adverse events or treatment noncompliance compared with empirical BQT. Therefore, we recommend tailored BQT based on fecal susceptibility testing as a first-line treatment. TRIAL REGISTRATION: EudraCT number: NCT05718609; ClinicalTrials.gov.