Efficacy of a 14-Day Bismuth-Containing Quadruple Therapy Guided by Drug Susceptibility Testing in Patients with Extremely Refractory Helicobacter Pylori Infection: an Exploratory Study

NCT06731023 | Not Yet Recruiting

• 1 other identifier: KYLL-202410-006-1
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Helicobacter pylori (H. pylori) infection, a prevalent global infectious disease, is a significant contributor to gastric cancer and other morbidities, imposing a substantial disease burden. With the rise in antibiotic resistance, the eradication of H. pylori is encountering formidable challenges. A subset of individuals, despite undergoing multiple treatment regimens, remain unable to successfully eradicate the infection. The persistence of infection in these cases could be attributed to either the limitations of detection methods leading to false positives or to the infection by superbugs that are highly resistant to antibiotics. This study is designed to ascertain whether these patients are infected with superbugs by employing various diagnostic techniques. Additionally, it aims to assess the antibiotic resistance profiles of strains associated with extremely refractory H. pylori infections through drug susceptibility testing. Based on the identified sensitivities, the study seeks to tailor treatment protocols with bismuth-containing quadruple therapy (Containing two kinds of antibiotics: sensitive antibiotic, rifabutin or high-dose metronidazole), to explore novel therapeutic strategies for patients with highly resistant H. pylori infections.

Conditions

HELICOBACTER PYLORI INFECTIONS

Keywords

Helicobacter pylori; Bismuth-Containing Quadruple Therapy; Drug Susceptibility Testing

Outcome Measures

Primary Outcomes (1)

• Eradication rate

  Immediately after follow-up check.

Secondary Outcomes (4)

• Rate of adverse reactions.

  Immediately after follow-up check.

• False positive rate

  Immediately after follow-up check.

• Patient compliance

  Immediately after follow-up check.

• Cost-effectiveness index

  Immediately after follow-up check.

Study Arms (3)

Unsuccessful culture attempts group

Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)

Drug: Bismuth; Drug: Vonoprazan; Drug: Amoxicillin; Drug: Rifabutin

Demonstrate sensitivity to both amoxicillin and rifabutin group

Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)

Drug: Bismuth; Drug: Vonoprazan; Drug: Amoxicillin; Drug: Rifabutin

Drug susceptibility testing group

Two non-resistant antibiotics are selected based on drug susceptibility testing outcomes. If a patient shows sensitivity to only one antibiotic, a combination of that sensitive antibiotic with high-dose metronidazole is administered.

Drug: Bismuth; Drug: Vonoprazan; Drug: Amoxicillin; Drug: Rifabutin; Drug: Metronidazole; Drug: Other antibiotics

Interventions

Bismuth DRUG

Bismuth 0.6g bid

Demonstrate sensitivity to both amoxicillin and rifabutin group; Drug susceptibility testing group; Unsuccessful culture attempts group

Vonoprazan DRUG

vonoprazan 20mg bid

Demonstrate sensitivity to both amoxicillin and rifabutin group; Drug susceptibility testing group; Unsuccessful culture attempts group

Amoxicillin DRUG

Amoxicillin 1g bid

Demonstrate sensitivity to both amoxicillin and rifabutin group; Drug susceptibility testing group; Unsuccessful culture attempts group

Rifabutin DRUG

Rifabutin 0.15g bid

Demonstrate sensitivity to both amoxicillin and rifabutin group; Drug susceptibility testing group; Unsuccessful culture attempts group

Metronidazole DRUG

Metronidazole 400mg qid

Drug susceptibility testing group

Other antibiotics DRUG

The selection of other antibiotics is based on the results of drug susceptibility testing.

Drug susceptibility testing group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study enrolled patients with extremely refractory Helicobacter pylori (H. pylori) infection, identified in the outpatient department. These patients had previously undergone eradication programs that included three antibiotics with low resistance rates: amoxicillin, tetracycline, and furazolidone. Despite this, reexamination confirmed persistent H. pylori infection. Upon entry into the study, participants were required to fulfill the inclusion criteria, not meet the exclusion criteria, and provide signed informed consent.

You may qualify if:

• Patients aged 18-65.
• Patients with H.pylori infection (Positive for rapid urease test or 13C urea breath test).
• Received at least two previous standard treatment protocols for Helicobacter pylori, and the application regimens included at least three low-resistance antibiotics.

You may not qualify if:

• Patients with serious underlying diseases, such as liver insufficiency, renal insufficiency, immunosuppression, malignant tumors, Coronary heart disease or coronary artery stenosis ≥75%.
• Patients who are pregnant or lactating or unwilling to take contraceptive measures during the trial.
• Patients with active gastrointestinal bleeding.
• Patients with a history of upper gastrointestinal surgery.
• Patients allergic to treatment drugs.
• Patients with medication history of bismuth agents, antibiotics, proton pump inhibitor and other drugs within 4 weeks
• Patients with other behaviors that may increase the risk of illness, such as alcohol and drug abuse
• Patients who are unwilling or incapable to provide informed consents.

Sponsors & Collaborators

• Xiuli Zuo: lead

Study Sites (1)

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

Location

Biospecimen

Retention: SAMPLES WITH DNA

Gastric mucosa samples, stool samples, and breath samples obtained during the study will be stored in a specific storage location for 10 years after the study is completed, and then completely deleted after 10 years.

MeSH Terms

Interventions

Bismuth; 1-(5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl)-N-methylmethanamine; Amoxicillin; Rifabutin; Metronidazole

Intervention Hierarchy (Ancestors)

Elements, Radioactive; Elements; Inorganic Chemicals; Metals, Heavy; Radioisotopes; Isotopes; Metals; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Nitroimidazoles; Nitro Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Xiuli Zuo, MD,PhD

CONTACT

15588818685; zuoxiuli@sdu.edu.cn

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Director of gastroenterology department of Qilu hospital.

Study Record Dates

• First Submitted: December 8, 2024
• First Posted: December 12, 2024
• Study Start: January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 19, 2024

Record last verified: 2024-12

Locations

CN (1)