Susceptibility-guided Bismuth Quadruple Therapy for Multiple-resistant Helicobacter Pylori Strains

NCT ID: NCT06687473

Last Updated: 2024-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-01
• Study Completion Date: 2023-03-31

Brief Summary

The goal of this clinical trial is to learn if the 14-day susceptibility-guided bismuth quadruple therapy works to treat multiple drug resistant Helicobacter pylori (H. pylori) in adults. It will also learn about the adverse effects of bismuth quadruple therapy. The main questions it aims to answer are:

• Does 14-day susceptibility-guided bismuth quadruple therapy higher the eradication rate?
• What medical problems do participants have when taking 14-day susceptibility-guided bismuth quadruple?
• Does bismuth suppress the expression of virulence factors of H. pylori?

Researchers will record 14-day susceptibility-guided bismuth quadruple to see if 14-day susceptibility-guided bismuth quadruple works to treat multiple drug resistant H. pylori.

Participants will:

• Take susceptibility-guided bismuth quadruple every day for 14 days
• Visit the clinic once 4-6 weeks for checkups and tests
• Keep a diary of their symptoms during taking susceptibility-guided bismuth quadruple

Detailed Description

Helicobacter pylori (H. pylori) infection is the major culprit of dyspeptic symptoms, peptic ulcer disease, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma. The Tokyo consensus stated that infection with H. pylori should be regarded as a pathogenic infectious disease rather than commensals only and should be eradicated.

H. pylori eradication regimen evolved with the increase of resistance rate in different regions. In Taiwan, clarithromycin resistance rate is arising from 9.5% in 2009 to around 14-17% in 2016 when conducting the first-line therapy. As a result, Taiwan gastroenterological association consensus suggested using 14-day clarithromycin-based (hybrid, sequential, concomitant, or triple) therapy as the first-line therapy and levofloxacin-based therapy as the second line therapy according to endemic resistance rate.

After twice eradication failure, H. pylori culture for susceptibility test is strongly recommended, which guide clinician to choose appropriate susceptibility-based therapy. Progressive increased dual (clarithromycin and levofloxacin) resistance and triple (dual and metronidazole) resistance, however, made it difficult for eradication. The regimens at physicians' discretion varied a lot and the overall successful eradication rate around 60% was still unsatisfactory.

Susceptibility-guided therapy is currently the consensus recommendation for 3rd-line H. pylori eradication. Bismuth quadruple therapy could overcome either clarithromycin or metronidazole resistant strains. Several evidences of clinical randomized-controlled trials demonstrated that adding bismuth as the first line therapeutic regimen can capture additional 30-40% successful eradication rate for the resistant strain, further contributing to the overall eradication rate. Accordingly, the aim of our study was to validate the susceptibility-guided bismuth quadruple therapy in patients with multiple drug resistant H. pylori infection in terms of efficacy and side effects.

Almost more than 99.5% ingested bismuth salt can be excreted from intestinal lumen without absorption. Bismuth may be able to form complexes in bacterial wall and periplasmic space, as well as inhibits enzymes, ATP synthesis and bacterial adherence to gastric mucosa. The MIC90 of bismuth to Helicobacter pylori ranged from 4-32 ng/L and there was no resistance been reported. Lots of H. pylori virulence factors are important players to establish colonization in gastric environment in each steps. Urease activity adjusts the pericellular environment to less acidity. Flagella direct bacterial motility and chemotaxis to mucosal surface. Colonization to epithelium is facilitated by lots of adhesion-receptor interaction, including BabA to Lewis B, SabA to sialyl-Lewis X, and CagL to α5β1 integrin. Bismuth drugs may affect the urease activity in jack bean plant and Klebsiella aerogenes. Bismuth inactivates H. pylori nickel-responsive transcription factor (NikR) protein, an important regulator for nickel homeostasis and iron metabolism in H. pylori. Since nickel iron is crucial in the catalytic function of urease, it is reasonable to assuming that it may impose effect on the urease activity in H. pylori. Furthermore, a pilot study showed that nickel-free diet can enhance the H. pylori eradication rate, which was speculated due to decreased urease activity.

Conditions

Helicobacter Pylori; Drug Resistance, Multiple; Virulence Factor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bismuth-based susceptibility-guided treatment

Participants who have triple- or quadruple-drug resistant H. pylori infection are enrolled. Participants receive one of the four regimens based on susceptibility test.

Group Type: EXPERIMENTAL

Bismuth-based susceptibility-guided treatment

Intervention Type: DRUG

The investigators design four regimes for H. pylori eradication and participants receive one of the regimens based on susceptibility test. The four regimens are PBAT for those with both amoxicillin and tetracycline susceptible H. pylori; PBAM for those with amoxicillin susceptible but tetracycline resistant H. pylori; PBMT for those with amoxicillin resistant but tetracycline susceptible H. pylori; PBMR for those with both amoxicillin and tetracycline resistant H. pylori.

A is amoxicillin (1000 mg thrice daily), B is colloidal bismuth subcitrate (120 mg thrice daily), M is metronidazole (500 mg thrice daily), P is a proton pump inhibitor, i.e., esomeprazole (40 mg twice daily), R is rifabutin (150 mg twice daily), and T is tetracycline (500 mg thrice daily). The treatment duration is 14 days for all regimens.

Interventions

Bismuth-based susceptibility-guided treatment

The investigators design four regimes for H. pylori eradication and participants receive one of the regimens based on susceptibility test. The four regimens are PBAT for those with both amoxicillin and tetracycline susceptible H. pylori; PBAM for those with amoxicillin susceptible but tetracycline resistant H. pylori; PBMT for those with amoxicillin resistant but tetracycline susceptible H. pylori; PBMR for those with both amoxicillin and tetracycline resistant H. pylori.

A is amoxicillin (1000 mg thrice daily), B is colloidal bismuth subcitrate (120 mg thrice daily), M is metronidazole (500 mg thrice daily), P is a proton pump inhibitor, i.e., esomeprazole (40 mg twice daily), R is rifabutin (150 mg twice daily), and T is tetracycline (500 mg thrice daily). The treatment duration is 14 days for all regimens.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• H. pylori-infected with treatment experience with at least one course of eradication failure
• H. pylori-infected with treatment naïve but having multiple-drug resistant H. pylori (>= three antibiotics)
• H. pylori infection confirmed by H. pylori culture

Exclusion Criteria

• Previous allergic reactions to regimens, including amoxicillin, bismuth subcitrate, esomeprazole, metronidazole, rifabutin, and tetracycline,
• Severe comorbidities,
• Chronic kidney disease with estimated glomerular filtration rate < 60 ml/min/1.73 m2,
• Pregnant or breastfeeding women.
• Dual-resistant H. pylori infection
• Mono-resistant H. pylori infection
• All susceptible H. pylori infection
• Positive RUT but negative H. pylori culture
• Negative RUT and negative H. pylori culture
• Decline to participate

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cheng-Kung University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Hsiu-Chi Cheng, MD, PhD

Role: STUDY_DIRECTOR

National Cheng-Kung University Hospital

Locations

National Cheng Kung University Hospital

Tainan City, Taiwan, Taiwan

Countries

Taiwan

References

Fischbach L, Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Aliment Pharmacol Ther. 2007 Aug 1;26(3):343-57. doi: 10.1111/j.1365-2036.2007.03386.x.

Reference Type: BACKGROUND

PMID: 17635369 (View on PubMed)

Other Identifiers

B-BR-110-096

Identifier Type: -

Identifier Source: org_study_id