Intensified Acid Suppression Strategy for Optimizing Helicobacter Pylori Eradication Regimen Duration and Drug Combination: A Multicenter, Open-Label, Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 316
- 主要终点
- H. pylori Eradication Rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •Risk behaviors such as drug abuse or alcohol dependence.
- •Pregnancy, breastfeeding, or unwillingness to use contraception during the study period.
- •Current use of atazanavir sulfate or rilpivirine hydrochloride at screening.
- •Requirement during the 14-day treatment period for any of the following medications: ergotamine, dihydroergotamine, probenecid, allopurinol, or methotrexate.
- •Inability or unwillingness to provide informed consent.
研究组 & 干预措施
High-Dose Keverprazan Dual Therapy for 10 Days
Keverprazan 20 mg tid Minocycline 100 mg bid (All medications administered orally for 10 consecutive days)
干预措施: Keverprazan Hydrochloride 20 mg TID (Drug)
High-Dose Keverprazan Dual Therapy for 10 Days
Keverprazan 20 mg tid Minocycline 100 mg bid (All medications administered orally for 10 consecutive days)
干预措施: Minocycline 100 mg (10-Day Regimen) (Drug)
Keverprazan-Based Quadruple Therapy for 14 Days
Keverprazan 20 mg bid Bismuth Potassium Citrate 240 mg bid Amoxicillin 1000 mg bid Minocycline 100 mg bid (All medications administered orally for 14 consecutive days.)
干预措施: Keverprazan Hydrochloride 20 mg BID (Drug)
Keverprazan-Based Quadruple Therapy for 14 Days
Keverprazan 20 mg bid Bismuth Potassium Citrate 240 mg bid Amoxicillin 1000 mg bid Minocycline 100 mg bid (All medications administered orally for 14 consecutive days.)
干预措施: Bismuth Potassium Citrate 240 mg (Drug)
Keverprazan-Based Quadruple Therapy for 14 Days
Keverprazan 20 mg bid Bismuth Potassium Citrate 240 mg bid Amoxicillin 1000 mg bid Minocycline 100 mg bid (All medications administered orally for 14 consecutive days.)
干预措施: Minocycline 100 mg (14-Day Regimen) (Drug)
Keverprazan-Based Quadruple Therapy for 14 Days
Keverprazan 20 mg bid Bismuth Potassium Citrate 240 mg bid Amoxicillin 1000 mg bid Minocycline 100 mg bid (All medications administered orally for 14 consecutive days.)
干预措施: Amoxicillin 1000 mg (Drug)
结局指标
主要结局
H. pylori Eradication Rate
时间窗: 6 weeks post-treatment
The proportion of participants achieving successful H. pylori eradication, defined as a negative 13C-urea breath test result, assessed at 6 weeks after completion of treatment.
次要结局
- Incidence of Adverse Events(From first dose to 6 weeks post-treatment)
- Treatment Adherence Rate(At the end of treatment (Day 10+3 for Arm A; Day 14+3 for Arm B))
研究者
Yueyue Li
associate chief physician
Qilu Hospital of Shandong University