Optimizing Duration and Dosing Frequency of Vonoprazan–Amoxicillin Dual Therapy for Helicobacter pylori: A Multicenter Randomized Trial

BACKGROUND: A 10 day vonoprazan-amoxicillin (VA) regimen (amoxicillin 750 mg four times daily) achieved > 90% Helicobacter pylori (H. pylori) eradication rates in the initial treatment. Whether less frequent dosing or shorter duration provides comparable efficacy remains unclear. This study aimed to evaluate the efficacy of simplified 7 or 10-day VA regimens to determine the optimal first-line strategy. METHODS: In this multicenter, randomized, open-label, non-inferiority trial, treatment-naive H. pylori-positive patients were randomly assigned (1:1:1:1) to four treatment groups: VA-T7 (amoxicillin 1000 mg three times daily for 7 days), VA-Q7 (amoxicillin 750 mg four times daily for 7 days), VA-T10 (amoxicillin 1000 mg three times daily for 10 days), and VA-Q10 (amoxicillin 750 mg four times daily for 10 days). All the patients received vonoprazan 20 mg twice daily. The primary outcome was the eradication rate. The secondary outcomes included adverse events and adherence. RESULTS: A total of 500 patients were enrolled. The eradication rates of the VA-T7, VA-Q7, VA-T10, and VA-Q10 groups were 84.0%, 81.6%, 91.2%, and 90.4% by intention-to-treat (ITT) analysis; 86.8%, 83.6%, 92.7%, and 92.6% by modified intention-to-treat (mITT) analysis; 88.2%, 85.7%, 93.4%, and 94.1% by per-protocol (PP) analysis, respectively. The efficacy of VA-T10 was non-inferior to that of VA-Q10 (p = 0.002; p = 0.001; p = 0.002 in the ITT, mITT and PP analyses, respectively). Both 7-day regimens failed to meet the non-inferiority margin of -10%. No significant effect of dosing frequency on eradication rates was observed. Adverse events and adherence were comparable among the groups. CONCLUSIONS: The VA-T10 regimen is effective, well-tolerated, and suitable for first-line H. pylori eradication, whereas 7-day regimens are not recommended due to eradication rates < 90%. TRIAL REGISTRATION: ClinicalTrials.gov identifier: ChiCTR2400079754 (www.chictr.org.cn).