Background:
Helicobacter pylori (H. pylori) infection affects approximately 50% of the global population and is closely associated with chronic gastritis, peptic ulcer disease, and gastric cancer. Eradication of H. pylori can reduce the overall risk of gastric cancer by 39%. Current international guidelines recommend bismuth-containing quadruple therapy as first-line treatment; however, its complex regimen, adverse effects, cost, and suboptimal patient adherence limit its clinical application. Potent acid suppression is essential for H. pylori eradication, as maintaining an intragastric pH of 6-8 enhances the stability of acid-labile antibiotics and promotes bacterial replication, thereby increasing antibiotic susceptibility. Potassium-competitive acid blockers (P-CABs), such as vonoprazan, provide rapid, potent, and sustained acid suppression with dose-dependent effects. Keverprazan hydrochloride is a novel P-CAB with demonstrated dose-dependent acid suppression and favorable safety profiles in Phase I and Phase III studies. Whether an intensified P-CAB dosing strategy can allow treatment shortening and regimen simplification while maintaining high eradication rates warrants investigation.
Objective:
To evaluate the efficacy and safety of a 10-day high-dose keverprazan dual therapy versus a standard 14-day keverprazan-based bismuth quadruple therapy for first-line H. pylori eradication.
Study Design:
This is a multicenter, open-label, randomized controlled trial. Eligible participants (aged 18-70 years with confirmed H. pylori infection and no prior eradication history) will be randomly assigned in a 1:1 ratio to one of two treatment arms:
Arm A (Dual therapy, 10 days): Keverprazan 20 mg three times daily plus minocycline 100 mg twice daily.
Arm B (Quadruple therapy, 14 days): Keverprazan 20 mg twice daily, bismuth potassium citrate 240 mg twice daily, amoxicillin 1000 mg twice daily, and minocycline 100 mg twice daily.
The primary efficacy assessment will be performed at 6 weeks post-treatment using the 13C-urea breath test. A total of 316 participants (158 per arm) will be enrolled, accounting for an estimated 10% dropout rate.
Outcome Measures:
Primary Outcome: H. pylori eradication rate at 6 weeks after completion of treatment.
Secondary Outcomes: Safety and tolerability (adverse events, laboratory abnormalities) and treatment adherence.
Aged 18 to 70 years, male or female.
Confirmed H. pylori infection, defined as a positive 13C-urea breath test (13C-UBT) plus at least one positive result from the following: stool H. pylori antigen test, rapid urease test, or gastric mucosal histopathology.
No prior history of H. pylori eradication therapy.
Known allergy or hypersensitivity to any of the study drugs (keverprazan, amoxicillin, minocycline, bismuth).
Acute upper gastrointestinal bleeding, active gastric or duodenal ulcer, acute gastric mucosal injury, or acute duodenal mucosal injury at screening.
Severe underlying diseases, including: hepatic or renal insufficiency; immunosuppression; malignancy; severe central nervous system, cardiovascular, or respiratory diseases.
Use of antibiotics, bismuth-containing preparations, or Chinese herbal medicines with antimicrobial effects within 4 weeks prior to the screening 13C-UBT; use of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (P-CABs) within 2 weeks prior to the screening 13C-UBT.