Optimizing H. Pylori Eradication Regimen Under Intensified Acid Suppression

Summary

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.

Conditions

• HELICOBACTER PYLORI INFECTIONS

Interventions

DRUG

Keverprazan Hydrochloride 20 mg TID

Participants will receive keverprazan hydrochloride 20 mg orally three times daily for 10 days.

DRUG

Minocycline 100 mg (10-Day Regimen)

Participants will receive minocycline 100 mg orally twice daily for 10 days.

DRUG

Keverprazan Hydrochloride 20 mg BID

Participants will receive keverprazan hydrochloride 20 mg orally twice daily for 14 days.

DRUG

Bismuth Potassium Citrate 240 mg

Participants will receive bismuth potassium citrate 240 mg orally twice daily for 14 days.

DRUG

Amoxicillin 1000 mg

Participants will receive amoxicillin 1000 mg orally twice daily for 14 days.

DRUG

Minocycline 100 mg (14-Day Regimen)

Participants will receive minocycline 100 mg orally twice daily for 14 days.

Sponsors & Collaborators

• Qilu Hospital of Shandong University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-08-01

Primary Completion

2028-07-10

Completion

2028-08-10