Efficacy and safety of vonoprazan, amoxicillin, and berberine hydrochloride triple therapy as first-line Helicobacter pylori eradication therapy

Helicobacter pylori (H. pylori) remains one of the most prevalent bacterial infections worldwide, with a global prevalence rate of approximately 50%. Chronic H. pylori infection is closely associated with the development and progression of a wide spectrum of digestive disorders, including peptic ulcer disease, chronic gastritis, and gastric cancer. However, as antibiotic resistance rates continue to rise year by year, the eradication efficacy of current first-line therapies has been steadily declining, presenting a growing challenge to clinical management. In China, the resistance rate to clarithromycin—one of the most commonly used first-line antibiotics for H. pylori eradication—exceeds 15% in most provinces, significantly impairing the effectiveness of standard bismuth quadruple therapy. Additionally, the insufficient acid-suppressing efficacy of traditional proton pump inhibitors (PPIs) represents another important factor contributing to eradication failure. Therefore, exploring alternative antimicrobial agents with low resistance rates and potent acid-suppressing effects has become a top priority for optimizing current clinical treatment strategies. 

To address this clinical need, Professor Yongquan Shi and Professor Min Chen from the State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases, The First Affiliated Hospital, Air Force Medical University, China, along with a team of researchers, conducted a prospective, noninferiority, open-label randomized controlled trial (RCT) to evaluate the efficacy and safety of triple therapy comprising vonoprazan, amoxicillin, and berberine hydrochloride versus esomeprazole-based bismuth quadruple therapy for the initial eradication of H. pylori. Their findings were published online on September 14, 2026, in the Chinese Medical Journal. The study enrolled 558 treatment-naïve patients aged 18–70 years with confirmed H. pylori infection, who were randomly assigned in a 1:1 ratio to either the experimental group (VAB group: vonoprazan 20 mg, amoxicillin 1,000 mg, and berberine hydrochloride 500 mg, twice daily) or the control group (EACB group: esomeprazole 40 mg, amoxicillin 1,000 mg, clarithromycin 500 mg, and colloidal bismuth tartrate 220 mg, twice daily), with a treatment duration of 14 consecutive days. The primary outcome was the H. pylori eradication rate 4 weeks after treatment completion, as confirmed by negative results on the 13C/14C urea breath test or stool antigen test. The study was approved by the Ethics Committee of the First Affiliated Hospital of Air Force Medical University (Approval No.: KY20242226-C-1) and registered on ClinicalTrials.gov (NCT06514274). 

The novel triple therapy achieved noninferior efficacy. In the intention-to-treat (ITT) analysis, eradication rates were 70.6% (197/279) in the VAB group versus 73.5% (205/279) in the EACB group; in the per-protocol (PP) analysis, 82.8% (197/238) versus 84.7% (205/242). No statistically significant differences were observed in either analysis set (P > 0.05), and the lower bounds of the 95% confidence intervals exceeded the−10% noninferiority margin, confirming noninferiority. Subgroup analyses revealed that age, smoking status, and alcohol consumption significantly affected eradication rates in the EACB group but not in the VAB group, with smoking identified as a significant negative predictor of treatment outcome in the quadruple therapy group. 

Overall adverse event rates were comparable between groups (26.5% vs. 25.4%, P = 0.772). Nausea (12.9% vs. 5.7%) and abdominal pain (3.2% vs. 0.7%) were more frequent in the VAB group, while bitter taste was significantly more common in the EACB group (3.6% vs. 15.4%, P < 0.001). All adverse events were mild to moderate and resolved spontaneously without intervention. Medication adherence was also similar between the two groups (94.6% vs. 95.7%, P = 0.339). 

"The efficacy of triple therapy consisting of vonoprazan, berberine hydrochloride, and amoxicillin for the initial eradication of H. pylori is noninferior to that of esomeprazole-based quadruple therapy, with favorable medication adherence and safety profiles," explains Prof. Shi. "This novel triple therapy provides an effective and safe alternative treatment option for the initial eradication of H. pylori, holding promise for clinical application and popularization, particularly in regions with high clarithromycin resistance rates." The study acknowledges certain limitations, including its single-center design which may introduce geographic bias, and the absence of H. pylori antibiotic susceptibility testing or analysis of individual differences such as host genetic polymorphisms. The researchers note that future studies should verify the therapeutic effects of both regimens through multidimensional data integration. 

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Reference 
DOI:  10.1097/CM9.0000000000004236 

About Professor Yongquan Shi from Air Force Medical University 
Dr. Shi Yongquan is the Chief Physician, Professor, and PhD Supervisor of the Department of Gastroenterology at the First Affiliated Hospital of the Air Force Medical University. His research focuses on Helicobacter pylori infection, gastrointestinal cancers, and digestive disease epidemiology. Prof. Shi has led multiple clinical trials evaluating novel therapeutic regimens for H. pylori eradication and published over 100 SCI papers as the first or corresponding author in journals such as Gut, Cancer Research, and Journal of Cell Biology. 

Funding information 
Noncommunicable Chronic Diseases-National Science and Technology Major Project (2025ZD0545301).