Vonoprazan-Amoxicillin Dual Sequential Therapy For Helicobacter Pylori-infected Treatment-naive Patients：A Randomized, Open-label, Parallel-controlled , Multicenter Clinical Trial

Helicobacter pylori (HP) is a Gram-negative, spiral-shaped, microaerophilic bacterium that colonizes the gastric mucosa. HP infection is a key pathogenic factor for peptic ulcers and chronic active gastritis and is closely associated with the development of gastric cancer and mucosa-associated lymphoid tissue lymphoma. Eradicating HP can effectively control disease progression and reduce the risk of related diseases. However, the increasing global antibiotic resistance poses significant challenges to HP eradication, necessitating further exploration of treatment regimens.

Dual therapy was first proposed in the late 1980s for treating HP infection. Given the pH-dependent and time-dependent antibacterial effects of amoxicillin on HP, recent improvements to dual therapy have focused on increasing drug dosage and administration frequency. A 2019 randomized controlled trial in China, including 232 patients, found that the modified dual therapy achieved similar eradication rates to bismuth quadruple therapy but with lower incidence of side effects and treatment costs. The 2022 Chinese guidelines for HP infection treatment recommend bismuth quadruple therapy and high-dose amoxicillin combined with proton pump inhibitors (PPI) as first-line eradication regimens.

Vonoprazan, a novel potassium-competitive acid blocker, offers stronger and more sustained gastric acid suppression compared to traditional PPIs, enhancing the bactericidal effect of amoxicillin. Therefore, vonoprazan is considered a superior choice for dual therapy. A Chinese study showed that a 14-day regimen of vonoprazan (20mg bid) combined with amoxicillin (1.0g tid) achieved similar efficacy and safety to esomeprazole (20mg qid) combined with amoxicillin (750mg qid) (ITT eradication rates: 89% vs. 87.7%, PP eradication rates: 94.1% vs. 92.8%), suggesting it as a potential first-line therapy for HP infection. The 2024 ACG guidelines for HP infection treatment recommend vonoprazan-based dual therapy (20mg bid + 1g tid of amoxicillin for 14 days) as a first-line option.

Sequential therapy for HP infection was first proposed by Zullo et al. in 2000, comprising two phases: the first phase involves 5-7 days of PPI combined with one antibiotic, and the second phase involves 5-7 days of PPI combined with two antibiotics. Studies have shown that the ITT eradication rate for the traditional 14-day sequential therapy regimen is 90.7%, while the 10-day regimen shows a rate of 87.0%. Building on the traditional sequential therapy, the investigators propose a modified sequential therapy strategy. In the first phase, vonoprazan is combined with amoxicillin (1g bid), and in the second phase, the amoxicillin dosage is increased to 1g tid. The proposed regimen is as follows: Days 1-7, vonoprazan (20mg bid) + amoxicillin (1g bid); Days 8-14, vonoprazan (20mg bid) + amoxicillin (1g tid). This regimen combines the staged nature of sequential therapy with the advantages of high-dose dual therapy. The gradual increase in drug dosage may help patients adapt to higher doses while minimizing gastrointestinal discomfort (such as nausea, vomiting, and diarrhea), potentially improving tolerance, especially for those sensitive to antibiotics.

This study aims to evaluate the modified regimen of vonoprazan combined with high-dose amoxicillin in comparison to standard dual therapy (14-day regimen) in terms of HP eradication rates, efficacy, side effect incidence, and patient compliance. Additionally, a multicenter randomized controlled trial in China demonstrated that the 10-day regimen of vonoprazan (20mg bid) + amoxicillin (1g tid) is not inferior to quadruple therapy, with ITT eradication rates of 86% and 89.2%, respectively. Therefore, this study will further explore the impact of shortened treatment duration on the efficacy of the modified dual sequential therapy for HP eradication.