Tailored Therapy Guided by Antibiotic Genotypic Resistances and CYP2C19 Polymorphisms Detected From Fecal Specimens for the First‐Line Helicobacter pylori Eradication: A Randomized Controlled Trial

ABSTRACT Background Tailored therapy based on genetic testing of fecal samples is a promising method for Helicobacter pylori eradication, but relevant research is still lacking, and the effectiveness remains unclear. Objective This study conducted a randomized controlled trial to evaluate the efficacy, safety, and compliance of triple plus bismuth therapy (TBT) guided by clarithromycin and levofloxacin genotypic resistances and CYP2C19 polymorphisms from stool samples. A preliminary health economics analysis was also conducted. Design Six hundred and sixteen treatment‐naïve patients were randomly divided into tailored (individualized drug selection based on genetic testing for 7 or 14 days) and empiric (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days) TBT groups. Safety and compliance were assessed within 1–3 days after eradication. 13 C‐urea breath test was performed within 4–8 weeks after eradication to evaluate the therapeutic outcome. Results The eradication rates of the tailored TBT group were non‐inferior to those of the empiric TBT group [intention‐to‐treat analysis 87.7% vs. 80.8%, rate difference 6.8% (95% confidence interval 0.8%–12.9%); modified intention‐to‐treat analysis 93.4% vs. 86.8%, rate difference 6.7% (95% confidence interval 1.5%–11.9%); per‐protocol analysis 95.7% vs. 88.7%, rate difference 7.0% (95% confidence interval 2.2%–11.8%)]. The tailored TBT group achieved satisfactory efficacies (acceptable in intention‐to‐treat and excellent in per‐protocol analyses). Safety and compliance were similar between the two groups. The average cost of each successful eradication case in the tailored TBT group is lower than that in the empiric TBT group. Conclusion The tailored TBT guided by antibiotic genotypic resistances and CYP2C19 polymorphisms detected from fecal specimens achieved satisfactory efficacy, safety, and compliance in the first‐line Helicobacter pylori eradication with less expenses (ChiCTR2300068620). Trial Registration Chinese Clinical Trials Registration: ChiCTR2300068620