Vonoprazan-amoxicillin dual, rifabutin-based triple, and bismuth quadruple therapies for <i>Helicobacter pylori</i> rescue treatment: a multicentre, open-label, non-inferiority randomised trial.

Abstract

Whether vonoprazan-amoxicillin dual therapy (VA) or rifabutin-based triple study (VRA) can replace bismuth quadruple therapy (BQT) for <i>Helicobacter pylori</i> rescue treatment remains unclear. We aimed to evaluate the efficacy and safety of 10-day VA and VRA regimens, compared with BQT, for rescue therapy. We conducted an open-label, non-inferiority randomised controlled trial at three hospitals in China. Refractory <i>H. pylori</i>-infected patients with at least two previous treatment failures were randomly assigned (1:1:1; block sizes six) to 10 days vonoprazan-containing (20 mg twice daily) regimens of VA (amoxicillin 1000 mg three times daily); VRA (amoxicillin 1000 mg three times daily, and rifabutin 150 mg twice daily); or BQT (bismuth 110 mg, tetracycline 500 mg, and metronidazole 400 mg, all four times daily). The primary endpoint was <i>H. pylori</i> eradication rate evaluated by ¹³C-urea breath test. Adverse events were assessed in all patients. Non-inferiority margin was -10%. This trial is registered at ClinicalTrials.gov (NCT05874544). Between May 16, 2023, and Jan 31, 2025, 360 subjects (110 [31%] male and 250 [69%] female; mean age 48.4 years [SD 12.1]) were randomly assigned to VA, VRA or BQT (n = 120 per group). Intention-to-treat eradication rates were 75.8% (91/120; 95% CI 67.0-83.0) with VA, 90.0% (108/120; 95% CI 82.8-94.5) with VRA, and 90.8% (109/120; 95% CI 83.8-95.1) with BQT. Non-inferiority of VA to BQT was not established (difference -15.0%; 95% CI -24.2 to -5.8; p = 0.86), whereas VRA was non-inferior to BQT (difference -0.8%; 95% CI -8.3 to 6.6; p = 0.0078). Resistance rates for amoxicillin, rifabutin, tetracycline, and metronidazole were 10%, <1%, 0.0%, and 96%, respectively. Amoxicillin resistance, BMI ≥25 kg/m², and smoking reduced efficacy in the VA group only (p < 0.0001, p = 0.023, and p = 0.011, respectively). Adverse events occurred in 8% (10) of VA, 25% (30) of VRA, and 53% (64) of BQT; fever (10 [8%]) and neutropenia (16 [13%]) were more frequent with VRA. Ten-day VRA therapy is a viable alternative to BQT therapy for <i>H. pylori</i> rescue treatment with fewer adverse events, whereas VA therapy showed unacceptable efficacy. National Natural Science Foundation of China, and Xinyi Digestive Disease Fund Project, College of Digestive Sciences, Shanghai Jiao Tong University School of Medicine.