7-Day Vonoprazan, High-Dose Amoxicillin, and Bismuth Therapy

NCT ID: NCT07232095

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 316 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2027-06-30

Brief Summary

The 2024 American College of Gastroenterology (ACG) Clinical Guideline recommends a 14-day vonoprazan-amoxicillin (VA) regimen, consisting of vonoprazan 20 mg twice daily with amoxicillin 1000 mg three times daily, as a first-line treatment for Helicobacter pylori (H. pylori) infection.

Our previous study 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 exceeding 90%, with no significant difference between dosing frequencies. However, when the treatment duration was shortened to 7 days, both dosing schedules failed to reach satisfactory eradication rates, indicating a need for further optimization.

Bismuth has antibacterial and synergistic properties, such as disrupting bacterial membranes, suppressing protein synthesis, and reducing virulence factor expression. It may enhance the efficacy of antibiotics. Therefore, this study evaluated the efficacy and safety of a 7-day vonoprazan-high-dose amoxicillin-bismuth (VAB-7) regimen as a first-line treatment for H. pylori infection.

Eligible participants in this study will be randomly assigned to one of the following treatment groups based on a pre-generated randomization sequence:

Control Group: Vonoprazan combined with high-dose amoxicillin dual therapy for 14 days (VA-14): Vonoprazan 20mg twice daily + Amoxicillin 1g three times daily.

Experimental Group: Vonoprazan combined with high-dose amoxicillin and bismuth therapy for 7 days (VAB-7): Vonoprazan 20mg twice daily + Amoxicillin 1g three times daily+Bismuth 220mg twice daily.

Detailed Description

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.

This multicenter, randomized, controlled trial aims to compare the efficacy and safety of VAB-7 with the standard 14-day vonoprazan-high-dose amoxicillin dual therapy (VA-14). The primary endpoint is the eradication rate of H. pylori confirmed by a ¹³C-urea breath test performed at least 4 weeks after treatment completion. Secondary outcomes include adverse event rates, patient adherence, and cost-effectiveness.

Conditions

Helicobacter Pylori

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

7-day Vonoprazan-High-dose Amoxicillin-Bismuth therapy

Vonoprazan 20mg twice daily+Amoxicillin 1g three times daily+Bismuth 220mg twice daily for 7 days

Group Type: EXPERIMENTAL

VAB-7

Intervention Type: DRUG

Vonoprazan 20mg twice daily+Amoxicillin 1g three times daily+Bismuth 220mg twice daily for 7 days

14-day Vonoprazan-Amoxicillin dual therapy

Vonoprazan 20mg twice daily and Amoxicillin 1g three times daily for 14 days

Group Type: ACTIVE_COMPARATOR

VA-14

Intervention Type: DRUG

Vonoprazan 20mg twice daily and Amoxicillin 1g three times daily for 14 days

Interventions

VA-14

Vonoprazan 20mg twice daily and Amoxicillin 1g three times daily for 14 days

Intervention Type: DRUG

VAB-7

Vonoprazan 20mg twice daily+Amoxicillin 1g three times daily+Bismuth 220mg twice daily for 7 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Aged 18 to 70 years, regardless of sex.

2. Helicobacter pylori infection confirmed by ¹³C or ¹⁴C urea breath test within 1 month before enrollment.

3. Chronic gastritis with H. pylori infection confirmed by endoscopy within 3 months, meeting the indications for eradication therapy in the Sixth National Consensus Report on the Management of Helicobacter pylori Infection (China), and willing to receive eradication treatment.

4. No prior H. pylori eradication therapy.

5. Written informed consent before participation.

Exclusion Criteria

1. Known allergy or hypersensitivity to any study medication (vonoprazan, amoxicillin, or bismuth).

2. Use of potassium-competitive acid blockers (P-CABs), proton pump inhibitors (PPIs), H₂ receptor antagonists, antibiotics, bismuth preparations, or probiotics within 4 weeks before enrollment.

3. Pregnant or lactating women.

4. Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or anticoagulants during the study period.

5. Presence of serious comorbid conditions that may interfere with study evaluation, including significant cardiac, pulmonary, hepatic, renal, metabolic, or psychiatric disorders, or malignancy.

6. History of gastric or esophageal surgery.

7. Any condition or factor that may affect compliance or make it difficult for the subject to complete follow-up as required.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The First Affiliated Hospital with Nanjing Medical University

OTHER

Sponsor Role: lead

Responsible Party

Feng Ye

Associate professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

The First Affiliated Hospital with Nanjing Medical University

Nanjing, Jiangsu, China

Countries

China

Central Contacts

Feng Ye, PhD

Role: CONTACT

fengye@njmu.edu.cn

86+13815897873

Facility Contacts

Feng Ye, PhD

Role: primary

fengye@njmu.edu.cn

86+13815897873

Other Identifiers

2025JSHERO4

Identifier Type: -

Identifier Source: org_study_id