Vonoprazan-Tetracycline Dual Regimen as Rescue Therapy for Helicobacter pylori Infection: Randomized Controlled Trial

BACKGROUND & AIMS: Treatment of Helicobacter pylori infection after previous eradication failure remains challenging. This study evaluated the efficacy and safety of a vonoprazan-tetracycline (VT) dual regimen as a potential rescue therapy. METHODS: In this prospective, open-label, randomized controlled trial, H pylori-positive adults with at least 1 prior eradication failure were allocated 1:1 to VT dual therapy (vonoprazan [20 mg, twice a day] and tetracycline [500 mg, 3 times a day]), or bismuth quadruple therapy (BQT; lansoprazole [30 mg, twice a day], colloidal bismuth [150 mg, 3 times a day], tetracycline [500 mg, 3 times a day], and metronidazole [400 mg, 3 times a day]) for 14 days. The primary outcome was noninferiority in eradication rates between VT and BQT groups. Secondary outcomes assessed adverse effects in both groups. RESULTS: Of 350 randomized patients (175 per group), the eradication rates in the VT dual-therapy group and the BQT group were, respectively, 90.6% (154 of 170; 95% confidence interval [CI], 84.9%-94.4%) and 89.3% (151 of 169; 95% CI, 83.5%-93.4%) in modified intention-to-treat analysis (difference, 1.2%; 95% CI,-5.7% to 8.2%; noninferiority P = .0003), 91.1% (153 of 168; 95% CI, 85.4%-94.7%) and 92.2% (141 of 153; 95% CI, 86.4%-95.7%) in per-protocol analysis (difference, -1.1%; 95% CI, -7.8% to 5.6%; noninferiority P = .002), meeting the noninferiority criterion (P < .0125). Treatment-emergent adverse events were less frequent with dual therapy (10.9% vs 45.7%; P < .001), and no patient discontinued because of adverse events (0.0% vs 8.6%; P < .001). Adherence was higher with dual therapy (96.0% vs 87.4%; P = .006). CONCLUSIONS: VT dual therapy for 14 days is an effective and well-tolerated rescue regimen for H pylori infection. This simplified regimen achieved eradication rates noninferior to BQT while substantially reducing adverse events and improving adherence. Chinese Clinical Trial Registry: ChiCTR2400080705 (chictr.org.cn,).