Xijing Hospital: berberine-based triple therapy non-inferior to quadruple for H. pylori, 558 patients

A prospective, non-inferiority, open-label randomized controlled trial from Xijing Hospital (China) compared two first-line regimens for Helicobacter pylori. According to ovid.com, a triple therapy of vonoprazan, amoxicillin and berberine hydrochloride was non-inferior to a quadruple therapy based on esomeprazole for initial eradication of the infection ovid.comovid.comovid.comOpen source ↗. Patients were enrolled from September 2024 to May 2025, and 558 were included in the intention-to-treat analysis ovid.comovid.comovid.comOpen source ↗.

Background and trial design

H. pylori has a global prevalence of about 50%, and rising antibiotic resistance has steadily lowered the eradication rate of current first-line therapy, the authors write ovid.comovid.comovid.comOpen source ↗. Vonoprazan is a potassium-competitive acid blocker whose effect does not depend on CYP2C19 gene polymorphisms. Berberine hydrochloride inhibits the growth of H. pylori and, according to the authors, has a low resistance rate ovid.comovid.comovid.comOpen source ↗.

The trial enrolled treatment-naive patients aged 18–70 years with confirmed infection. Of 609 patients screened, 558 were randomized 1:1 ovid.comovid.comovid.comOpen source ↗. The VAB group received vonoprazan 20 mg, amoxicillin 1000 mg and berberine hydrochloride 500 mg twice daily. The EACB group received esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg and colloidal bismuth tartrate 220 mg twice daily. Both courses lasted 14 days ovid.comovid.comovid.comOpen source ↗.

The primary outcome was the eradication rate 4 weeks after treatment, confirmed by a negative 13C/14C urea breath test or stool antigen test. Non-inferiority was accepted if the lower bound of the 95% confidence interval for the difference exceeded −10% ovid.comovid.comovid.comOpen source ↗.

Results

In the intention-to-treat analysis, eradication was achieved in 70.6% (197/279) of the VAB group and 73.5% (205/279) of the EACB group ovid.comovid.comovid.comOpen source ↗. In the per-protocol analysis, which included 480 patients who completed the study, the rates were 82.8% (197/238) and 84.7% (205/242) ovid.comovid.comovid.comOpen source ↗. The differences were not statistically significant in either analysis, and the lower confidence bounds exceeded the −10% margin ovid.comovid.comovid.comOpen source ↗.

In univariable analysis of the per-protocol population, age, smoking and alcohol consumption significantly affected eradication in the EACB group but not in the VAB group ovid.comovid.comovid.comOpen source ↗. In regression analysis of the EACB group, smoking had a significant negative effect on the outcome ovid.comovid.comovid.comOpen source ↗.

The study was approved by the ethics committee of the First Affiliated Hospital of Air Force Medical University and registered on ClinicalTrials.gov (NCT06514274) ovid.comovid.comovid.comOpen source ↗.