Efficacy of a 7-day vonoprazan, sitafloxacin, and amoxicillin triple therapy as a fourth-line salvage regimen for refractory Helicobacter pylori infection

Abstract

Background: Treatment failure of three standard regimens for Helicobacter pylori infections has increased and represents a significant challenge. The VAS regimen, consisting of vonoprazan, amoxicillin, and sitafloxacin, represents a promising treatment option, supported by its strong acid suppression and broad-spectrum antimicrobial activity. Objectives: To evaluate the efficacy and safety of the VAS regimen as the fourth-line regimen for refractory H. pylori infection. Methods: This prospective single-arm study involved patients with H. pylori infection who had failed three standard regimens. Participants received VAS regimen; comprising vonoprazan 20 mg twice daily, amoxicillin 1000 mg twice daily, and sitafloxacin 100 mg twice daily for 7 days. Genotypic resistance was identified and CYP2C19 and CYP3A5 were studied. Eradication success was assessed using the 13C-urea breath test at 4-8 weeks post-therapy. Results: Twenty patients (mean age 64.4 ± 8.6 years) were enrolled. The eradication rate was 70.0% (95% confidence interval (CI): 45.7–88.1) in the intention-to-treat analysis and 68.42% (95% CI: 43.5–87.4) in the per-protocol analysis. Notably, genotypic resistance demonstrated 93.9% and 85.7% of levofloxacin and clarithromycin resistance respectively. Mild adverse events were reported by three patients (15%), including loose stools, nausea, and bloating. Neither antibiotic resistance nor CYP2C19 and CYP3A5 rapid metabolizer status was associated with eradication failure. Conclusion: The seven-day VAS regimen was well tolerated and demonstrated acceptably good efficacy as the fourth-line treatment for refractory H. pylori infection. The regimen offers a reasonably viable empirical rescue when lack of antibiotic susceptibility testing. Trial registration: Thai Clinical Trials Registry (Identifier: TCTR20211203002, December 3, 2021).