Vonoprazan-based triple therapy for Helicobacter pylori resistant to first-line regimens: A guideline-compliant 14-day multicenter study in Egypt

Abstract

BACKGROUND: The global rise in antibiotic resistance has severely compromised the efficacy of first-line Helicobacter pylori therapies, particularly in Egypt, where dual resistance to clarithromycin and levofloxacin exceeds 55 % and dual clarithromycin-metronidazole resistance occurs in over 35 %. Vonoprazan, a potassium-competitive acid blocker, provides more potent and sustained acid suppression than proton pump inhibitors, enhancing eradication outcomes. This study evaluated a 14-day vonoprazan-based triple therapy for dual-resistant H. pylori infections. METHODS: This multicenter, single-arm cohort study was conducted between January 2023 and January 2024. A total of 300 patients with endoscopically confirmed H. pylori infection and dual resistance to clarithromycin and levofloxacin were enrolled. Patients received vonoprazan 20 mg twice daily, amoxicillin 1 g twice daily, and metronidazole 500 mg twice daily for 14 days. Eradication was assessed by monoclonal stool antigen testing at 4 weeks and 3 months per Maastricht VI guidelines. Endoscopic subgroups were analyzed histologically per Sydney criteria. Symptoms, laboratory indices, and safety were monitored. RESULTS: Per-protocol eradication was 89.5 % (255/285) and intention-to-treat eradication was 82 % (246/300). Efficacy was consistent across endoscopic subgroups (atrophic gastritis 90 %; peptic ulcer 87 %; gastric polyps 83 %; all p > 0.15). Symptom prevalence markedly decreased at 3 months: abdominal pain (79-7 %), bloating (55-3 %), and early satiety (64 % to 3 %) (all p < 0.001). Laboratory improvements included reduced WBC (10.9-7.2 ×10 ³/µL), and increased hemoglobin (11.3-14.0 g/dL) and platelets (199.4-240.6 ×10 ³/µL) (all p < 0.001). Adverse events occurred in 10 % (30/300), mostly Grade 1-2 (dry mouth 4 %, bloating 3 %, rash 2 %); three patients (1 %) had Grade 3 events. Diabetic patients had lower eradication than non-diabetics (88 % vs 95 %, p = 0.02). CONCLUSION: Fourteen-day vonoprazan-amoxicillin-metronidazole achieved high eradication rates in dual-resistant H. pylori with substantial symptom and laboratory improvements and an acceptable safety profile. This regimen represents a viable salvage option where first-line therapies fail.