IDDF2024-ABS-0375 Multi-centre, open-label, randomized controlled trial of amoxicillin dosage in vonoprazan dual helicobacter pylori therapy: effects on cure rate, gut microbiota and antibiotic resistome

<h3>Background</h3> To investigate the amoxicillin dosage required to achieve high cure rates, we compared 2 and 3 grams of amoxicillin on the efficacy and safety of vonoprazan dual therapy. We also assessed the short-term effects of therapy on the gut microbiota and antibiotic resistome. <h3>Methods</h3> This was an open-label, randomised trial conducted in 12 centres in China. <i>H. pylori</i>-infected subjects without prior eradication therapy were randomly assigned to receive either vonoprazan (20 mg b.i.d.) with low (1 g b.i.d. or LVA) or high-dose amoxicillin (1 g t.i.d. or HVA) for 14 days. Gastric biopsies were collected during pretreatment to detect antibiotic resistance. Stool samples were collected for shotgun metagenomic sequencing. The primary outcome of this study was the eradication rate of <i>H. pylori</i> using both intention-to-treat and per-protocol analyses. The secondary outcomes included adverse events, adherence, antibiotic resistance rate and alterations of gut microbiota and antibiotic resistome. <h3>Results</h3> 504 patients were randomly assigned to LVA or HVA therapy (IDDF2024-ABS-0375 Figure 1). No infections were resistant to amoxicillin. The eradication rates were LVA = 85.3% and HVA = 86.5% (<i>p</i>=0.70) by intention to treat analysis and 88.8% and 92.4% (<i>p</i>=0.18) by per protocol analysis. The efficacy of LVA was non-inferior to HVA in intention to treat analysis (<i>p</i>=0.002) and per protocol analysis (<i>p</i>=0.009) (IDDF2024-ABS-0375 Figure 2). 31 patients (12%) in the LVA group and 43 patients (17%) in the HVA group reported adverse events (<i>p</i>=0.13). Adherence to therapy was 97% in the LVA group and 96% in the HVA group. The diversity of gut microbiota decreased after treatment but was restored to baseline at weeks 8-10 for both groups (IDDF2024-ABS-0375 Figure 3). The alpha diversity of total resistome was increased after treatment but was restored to pretreatment level at weeks 8-10 for both groups (IDDF2024-ABS-0375 Figure 4). <h3>Conclusions</h3> LVA therapy was effective and non-inferior to HVA dual therapy as the first-line treatment of <i>H. pylori</i> infection in China. Vonoprazan-amoxicillin dual therapy for 14 days had minimal effects on the gut microbiota and antibiotic resistome.