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

Not yet recruiting

• Conditions: HELICOBACTER PYLORI INFECTIONS
• Interventions: Drug: Bismuth; Drug: Vonoprazan; Drug: Amoxicillin; Drug: Rifabutin; Drug: Metronidazole; Drug: Other antibiotics

• Registration Number: NCT06731023
• Lead Sponsor: Xiuli Zuo

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.

Detailed Description

The study enrolled patients with extremely refractory Helicobacter pylori (H. pylori) infection, identified in the outpatient department. Following enrollment, a comprehensive diagnostic approach was employed to ascertain the presence of H. pylori infection and to rule out false positives. Patients who test truly positive for H. pylori should undergo eradication therapy, avoiding any previously administered regimens. For those with unsuccessful culture attempts, a bismuth-containing quadruple therapy (vonoprazan + bismuth + amoxicillin + rifabutin) is recommended as an exploratory approach. Patients with successful cultures should undergo drug susceptibility testing to identify antibiotic resistance patterns of the H. pylori strain. Based on these results, a 14-day course of bismuth-containing quadruple eradication therapy is prescribed. Patients with strains that demonstrate sensitivity to both amoxicillin and rifabutin are assigned to the bismuth-containing quadruple therapy group (vonoprazan + bismuth + amoxicillin + rifabutin). For other patients, two non-resistant antibiotics are selected based on drug susceptibility test outcomes. If a patient shows sensitivity to only one antibiotic, a combination of that sensitive antibiotic with high-dose metronidazole is administered. After eradication treatment, 13C urea breath test and fecal antigen detection were re-examined 4 weeks after drug withdrawal.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-08
• Study First Submitted QC: 2024-12-11
• Study First Posted: 2024-12-12
• Last Update Submitted: 2024-12-16
• Last Update Posted: 2024-12-19
• Study Start: 2025-01-01
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

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

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Unsuccessful culture attempts group	Bismuth	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Unsuccessful culture attempts group	Vonoprazan	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Unsuccessful culture attempts group	Amoxicillin	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Unsuccessful culture attempts group	Rifabutin	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Demonstrate sensitivity to both amoxicillin and rifabutin group	Bismuth	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Demonstrate sensitivity to both amoxicillin and rifabutin group	Vonoprazan	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Demonstrate sensitivity to both amoxicillin and rifabutin group	Amoxicillin	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Demonstrate sensitivity to both amoxicillin and rifabutin group	Rifabutin	Bismuth-containing quadruple therapy (vonoprazan 20 mg bid + bismuth 0.6g bid + amoxicillin 1g bid + rifabutin 0.15g bid)
Drug susceptibility testing group	Bismuth	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 susceptibility testing group	Vonoprazan	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 susceptibility testing group	Amoxicillin	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 susceptibility testing group	Rifabutin	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 susceptibility testing group	Metronidazole	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 susceptibility testing group	Other antibiotics	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.

Primary Outcome Measures

Name	Time	Method
Eradication rate	Immediately after follow-up check.

Secondary Outcome Measures

Name	Time	Method
Rate of adverse reactions.	Immediately after follow-up check.
False positive rate	Immediately after follow-up check.	The false positive rate is defined as the proportion of patients whose only C13 breath test results are positive and any other test is negative.
Patient compliance	Immediately after follow-up check.	Good compliance is defined as the actual dosage is within the range of 80%-100% of the dosage that should be taken.
Cost-effectiveness index	Immediately after follow-up check.	Ratio of costs to effectiveness

Trial Locations

Locations (1)

Qilu Hospital of Shandong University; 🇨🇳 Jinan, Shandong, China