Comparison of the efficacy of 14-day sequential therapy and 10-day bismuth quadruple therapy in the second line therapy for Helicobacter pylori infection- A multi-center randomized trial.

BACKGROUND: Whether extending treatment duration and using high-dose esomeprazole can improve the efficacy of sequential therapy as second-line treatment for Helicobacter pylori (H. pylori) infection remains uncertain. We aimed to compare the efficacy and tolerability of optimized 14-day sequential therapy (ST14) and 10-day bismuth quadruple therapy (BQ10), both containing high-dose esomeprazole, as second-line treatment after failure of standard triple therapy. METHODS: In this multicenter, open-label, randomized trial conducted at six hospitals in Taiwan, adult patients (≥20 years) with confirmed H. pylori infection who failed first-line standard triple therapy were randomly assigned to receive ST14 or BQ10. Both regimens included esomeprazole 40 mg twice daily. The primary outcome was eradication rate assessed by ^13C-urea breath test using intention-to-treat (ITT) and per-protocol (PP) analyses. Secondary outcomes included adverse events, treatment adherence, and short-term changes in metabolic parameters. Antibiotic resistance and 23S ribosomal RNA mutations were assessed in available isolates. CLINICALTRIALS: gov: NCT03208426. RESULTS: A total of 155 patients were randomized (ST14, n = 76; BQ10, n = 79). Eradication rates were significantly lower with ST14 than with BQ10 in both ITT analysis (60.5% vs. 87.3%, P < 0.0001) and PP analysis (62.2% vs. 98.6%, P < 0.0001). ST14 was associated with fewer adverse events than BQ10 (39.5% vs. 62.0%, P = 0.008), while treatment adherence was high and comparable between groups. The eradication rate of ST14 was 80% in strains harboring 23S ribosomal RNA mutations and 99% in those without mutations (P < 0.0001). No clinically meaningful differences in metabolic parameters were observed at 8 weeks. CONCLUSIONS: BQ10 provides superior eradication efficacy compared with ST14 as second-line treatment for H. pylori infection, despite higher rates of adverse events. Sequential therapy with high-dose esomeprazole should not be used empirically as second-line therapy.