7-Day Vonoprazan-High-Dose Amoxicillin-Bismuth Therapy for First-Line Eradication of Helicobacter Pylori: A Multicenter Randomized Controlled Trial

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that chronically colonizes the gastric mucosa, leading to persistent inflammation and mucosal injury. Eradication of H. pylori can prevent the recurrence of peptic ulcers, treat gastric mucosa-associated lymphoid tissue (MALT) lymphoma, and reduce the risk of gastric cancer. However, with the increasing prevalence of antibiotic resistance, eradication rates have gradually declined worldwide, creating an urgent need for more effective, safe, and practical treatment regimens.

In recent years, vonoprazan, a novel and potent potassium-competitive acid blocker (P-CAB), has emerged as an alternative to conventional proton pump inhibitors (PPIs). Its rapid onset and strong acid suppression provide an ideal environment for amoxicillin to maintain stable bactericidal activity. The vonoprazan-amoxicillin (VA) dual therapy has demonstrated excellent eradication efficacy and safety in several clinical studies and has been recommended by the 2024 American College of Gastroenterology (ACG) Clinical Guideline as a first-line treatment for H. pylori infection.

Our previous multicenter trial on regimen optimization showed that vonoprazan 20 mg twice daily combined with amoxicillin 1 g three times daily or 750 mg four times daily for 10 days achieved satisfactory eradication rates above 90%, with no significant difference between dosing frequencies. However, shortening the treatment duration to 7 days resulted in slightly lower eradication rates (below 90%), indicating that the shortened regimen may require further optimization to maintain high efficacy.

Bismuth compounds exhibit multiple antimicrobial and synergistic effects. They can inhibit H. pylori adhesion to the gastric mucosa, disrupt bacterial membrane integrity, suppress protein synthesis, and reduce the expression of virulence factors. In addition, bismuth enhances the activity of antibiotics such as amoxicillin by reducing bacterial resistance and increasing local drug concentration in the gastric mucosa. Previous studies have shown that 7-day bismuth-containing regimens(with amoxicillin and tetracycline) can achieve comparable eradication rates to 14-day regimens.

This study was designed to evaluate whether the addition of bismuth could improve the efficacy of a short-course vonoprazan-amoxicillin regimen. Specifically, the trial investigates the 7-day vonoprazan-high-dose amoxicillin-bismuth (VAB-7) regimen as a first-line treatment for H. pylori infection.