Clinical trial NCT06760065: Comparison of Keverprazan Hydrochloride-Amoxicillin Dual Therapy and Susceptibility-Guided Quadruple Therapy for Helicobacter Pylori Rescue Treatment
Official title: A Multicenter, Randomized Controlled Study Comparing Keverprazan Hydrochloride-Amoxicillin Dual Therapy and Susceptibility-Guided Quadruple Therapy in Helicobacter Pylori Rescue Treatment
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Helicobacter Pylori Infection Helicobacter Pylori Eradication Patient Education
Keywords: Helicobacter pylori
Keverprazan Hydrochloride
Susceptibility-guided therapy
Lead sponsor: Sixth Affiliated Hospital, Sun Yat-sen University
Sponsor class: OTHER
Collaborators: name: Guangzhou First People's Hospital
name: The Seventh Affiliated Hospital of Sun Yat-sen University
name: Longgang District People's Hospital of Shenzhen
name: Eighth Affiliated Hospital, Sun Yat-sen University
name: Bao'an District People's Hospital of Shenzhen
name: Foshan Fuxing Chancheng Central Hospital
First posted: 2025-01-06
Enrollment: 316
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study uses a parallel design, where participants are randomly assigned to one of two groups: (1) Keverprazan Hydrochloride combined with Amoxicillin as a dual therapy, or (2) a susceptibility-guided quadruple therapy. Each group will receive the assigned treatment independently, and outcomes will be compared to assess the efficacy and safety of both regimens. Randomization ensures balanced allocation, and the parallel model allows for direct comparison of the two interventions under controlled conditions.
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate the efficacy and safety of Keverprazan Hydrochloride combined with Amoxicillin in dual therapy compared to susceptibility-guided quadruple therapy in the treatment of Helicobacter pylori (H. pylori) infections requiring rescue therapy. H. pylori is a common infectious disease associated with peptic ulcers, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. However, the increasing resistance of H. pylori to antibiotics has reduced the eradication rates of standard therapies.

Potassium-competitive acid blockers (P-CABs), such as Keverprazan Hydrochloride, provide faster and more sustained gastric acid suppression compared to traditional proton pump inhibitors (PPIs), making them a promising option for H. pylori treatment. This multicenter, randomized controlled trial will provide critical evidence comparing the effectiveness of Keverprazan-based dual therapy to susceptibility-guided quadruple therapy, aiming to establish optimized rescue therapy guidelines for H. pylori eradication.

Detailed description: Helicobacter pylori (H. pylori) is a globally prevalent chronic infectious disease with an infection rate exceeding 50%. As a Gram-negative bacterium, H. pylori survives in the acidic gastric environment and is a major cause of peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Eradication of H. pylori can prevent the recurrence of peptic ulcers and reduce the risk of developing gastric cancer. However, increasing antibiotic resistance has significantly decreased the eradication rate of standard triple therapy to below 80%, posing a substantial challenge to effective H. pylori management.

This study focuses on evaluating a novel potassium-competitive acid blocker (P-CAB), Keverprazan Hydrochloride, in combination with Amoxicillin as dual therapy for H. pylori rescue treatment. P-CABs, including Keverprazan, offer rapid and sustained gastric acid suppression independent of CYP2C19 polymorphism, overcoming limitations of traditional proton pump inhibitors (PPIs). Recent studies have demonstrated the efficacy of P-CABs in first-line H. pylori treatment with high eradication rates and fewer side effects. However, evidence for their use in rescue therapy is currently lacking.

This multicenter, randomized controlled trial aims to compare the efficacy and safety of Keverprazan Hydrochloride-Amoxicillin dual therapy with susceptibility-guided quadruple therapy in patients requiring rescue treatment. The trial will involve patients with confirmed H. pylori infection who failed previous treatment regimens. The study's primary outcome is the eradication rate, and secondary outcomes include the incidence of adverse events and patient compliance.

This research is expected to provide critical evidence for the clinical application of Keverprazan Hydrochloride in H. pylori rescue therapy, potentially establishing it as an effective and patient-friendly treatment option.

Eligibility criteria: Inclusion Criteria:

1. Male or female participants aged ≥18 years and ≤75 years at the time of signing the informed consent.
2. Participants who have undergone at least one prior standard H. pylori eradication treatment but failed.
3. Current H. pylori infection confirmed by 13C-UBT, or H. pylori culture.
4. Participants who, in the investigator's opinion, are able to understand and comply with the study requirements.
5. Written informed consent and any required privacy authorization documents signed and dated before the initiation of any study procedures.
6. For women of childbearing potential with regular or potential sexual activity with non-sterilized male partners, agreement to use two effective methods of contraception from the time of informed consent until the end of the study.

Exclusion Criteria:

1. Presence of gastric or duodenal ulcer with current or recent bleeding as evidenced by endoscopy.
2. Confirmed gastric cancer by endoscopic biopsy.
3. Receipt of any investigational drug (including marketed drugs used in post-marketing studies) within 30 days prior to the screening period. Participants who failed screening and did not receive the investigational drug may be included.
4. Participants who are investigators, relatives of investigators, or otherwise have conflicts of interest or may be under pressure to participate.
5. History of cutaneous or systemic lupus erythematosus.
6. Clinical manifestations of upper or lower gastrointestinal bleeding within 4 weeks prior to randomization.
7. Diagnosis of Zollinger-Ellison syndrome or other gastric acid hypersecretory disorders.
8. Known allergy or hypersensitivity to Keverprazan Hydrochloride (including excipients), PPIs, amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, furazolidone, or excipients in 13C-UBT (mannitol, citric acid, or aspartame).
9. History of alcohol abuse, illicit drug use, or drug addiction within 12 months prior to screening, or weekly alcohol intake exceeding 21 units (1 unit = 12 oz/300 ml beer, 1.5 oz/25 ml spirits, or 5 oz/100 ml wine).
10. Use of antibiotics, bismuth agents, or antiprotozoal drugs within 30 days prior to 13C-UBT, or use of H2 receptor antagonists, PPIs, or interfering drugs (e.g., sodium succinate) within 14 days.
11. Concurrent use of drugs contraindicated with clarithromycin (e.g., colchicine, pimozide, ergot derivatives, tadalafil, terfenadine, astemizole, cisapride, simvastatin, lovastatin, atorvastatin, etc.)..Use of pravastatin, fluvastatin, or rosuvastatin is permitted but should be used with caution.
12. Concurrent use of strong CYP2C19 or CYP3A4 inhibitors or inducers (e.g., fluconazole, fluoxetine, fluvoxamine, ticlopidine, rifampin, ritonavir, itraconazole, ketoconazole, indinavir, nelfinavir, saquinavir, telithromycin).
13. History of surgeries affecting gastric acid secretion, such as gastric resection or vagotomy.
14. Significant central nervous, cardiovascular, hepatic, pulmonary, renal, metabolic, gastrointestinal, urological, reproductive, endocrine, or hematological disorders that may affect the study results or participant safety, as judged by the investigator.
15. History of any malignancy, including MALT lymphoma.
16. Need for hospitalization or surgery during the study or within 30 days prior to screening.
17. Diagnosis of AIDS or HIV infection.
18. Female participants who are pregnant, breastfeeding, planning to become pregnant, or planning to donate eggs during the study or within 4 weeks after the study.
19. Participants with negative H. pylori culture during the screening period.
20. Participants with prior P-CAB plus amoxicillin dual therapy.

Primary outcomes:
measure: Proportion of Participants with Successful Eradication of Helicobacter pylori
timeFrame: At least 4 weeks after the last dose of study medication
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: