Simplified Helicobacter pylori therapy for patients with penicillin allergy: a randomised controlled trial of vonoprazan-tetracycline dual therapy

Abstract

Background and aims: This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy.

Methods: In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects.

Results: 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI -4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modified intention-to-treat analysis (difference 1.5%; 95% CI -4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI -2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010).

Conclusions: VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT.

Trial registration number: ChiCTR2300074693.

Keywords: Helicobacter pylori - treatment.

Figure 1

Flow chart of screening and recruitment of study subjects. LBTM group: (or bismuth quadruple therapy group) quadruple therapy group including lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. VT group: dual therapy group including vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day for 14 days. Data are n (%), or mean (SD). Cigarette smoking was defined by consumed >5 cigarettes a day or >1 cigarette pack/week consumed in the past 6 months. Alcohol drinking was defined by > 50 g of alcohol/day consumed in the past 6 months. Family history of gastric cancer was defined as a family history of gastric cancer in a first-degree relative (such as parents, siblings or children), which is associated with double to triple the risk of gastric cancer. The severity of AE was graded as: mild: transient and well-tolerated; moderate: discomfort noticeably interfering with daily activities; severe: considerable interference with daily activities, or requiring hospitalisation, or resulting in a study-related death. AEs, adverse effects; ITT, intention-to-treat analysis; mITT, modified intention-to-treat analysis; PP, per-protocol analysis.