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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HELICOBACTER PYLORI INFECTIONS
• Intervention / Treatment: Drug: Bismuth; Drug: Vonoprazan; Drug: Amoxicillin; Drug: Rifabutin; Drug: Metronidazole; Drug: Other antibiotics

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 Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Xiuli Zuo, MD,PhD; Phone Number: 15588818685; Email: zuoxiuli@sdu.edu.cn

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Qilu Hospital of Shandong University
      • Contact: Xiuli Zuo, MD,PhD; Phone Number: 15588818685; Email: zuoxiuli@sdu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Bismuth 0.6g bid; Drug: Vonoprazan; vonoprazan 20mg bid; Drug: Amoxicillin; Amoxicillin 1g bid; Drug: Rifabutin; Rifabutin 0.15g bid
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; Bismuth 0.6g bid; Drug: Vonoprazan; vonoprazan 20mg bid; Drug: Amoxicillin; Amoxicillin 1g bid; Drug: Rifabutin; Rifabutin 0.15g bid
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; Bismuth 0.6g bid; Drug: Vonoprazan; vonoprazan 20mg bid; Drug: Amoxicillin; Amoxicillin 1g bid; Drug: Rifabutin; Rifabutin 0.15g bid; Drug: Metronidazole; Metronidazole 400mg qid; Drug: Other antibiotics; The selection of other antibiotics is based on the results of drug susceptibility testing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Eradication rate	Immediately after follow-up check.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient compliance	Good compliance is defined as the actual dosage is within the range of 80%-100% of the dosage that should be taken.	Immediately after follow-up check.
Cost-effectiveness index	Ratio of costs to effectiveness	Immediately after follow-up check.
Rate of adverse reactions.		Immediately after follow-up check.
False positive rate	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.	Immediately after follow-up check.

Collaborators and Investigators

• Sponsor: Xiuli Zuo

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: December 8, 2024
• First Submitted That Met QC Criteria: December 11, 2024
• First Posted (Actual): December 12, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Bismuth-Containing Quadruple Therapy; Drug Susceptibility Testing
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Infections; Communicable Diseases; Helicobacter Infections; Disease Susceptibility; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Antiprotozoal Agents; Antiparasitic Agents; Antacids; Antibiotics, Antitubercular; Antitubercular Agents; Metronidazole; Bismuth; Amoxicillin; Rifabutin; Anti-Bacterial Agents
• Other Study ID Numbers: KYLL-202410-006-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No