Helicobacter PyloriPhase 4BSUS-1NCT06687473
Susceptibility-guided Bismuth Quadruple Therapy for Multiple-resistant Helicobacter Pylori Strains
A Phase 4 study testing Bismuth-based susceptibility-guided treatment in people with Helicobacter Pylori and Drug Resistance, Multiple, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Helicobacter Pylori, Drug Resistance, Multiple, Virulence Factor
- What is being tested?
- Bismuth-based susceptibility-guided treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Jan 2022to 31 Mar 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- All susceptible H. pylori infection
- Positive RUT but negative H. pylori culture
- Negative RUT and negative H. pylori culture
- Decline to participate
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Study of Bismuth Salt Effect on the Virulence Factors of Helicobacter Pylori and Its Therapeutic Role for Multiple-resistant Strains
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?
Read more
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
Read the 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.
- 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.
- Being tested
- Bismuth-based susceptibility-guided treatment
- Keywords
- bismuth, microbial sensitivity tests, Helicobacter pylori, drug resistance, multiple, Virulence Factor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bismuth-based susceptibility-guided treatmentDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Bismuth-based susceptibility-guided treatment | Experimental | Participants who have triple- or quadruple-drug resistant H. pylori infection are enrolled. Participants receive one of the four regimens based on susceptibility test. Receives: Drug: Bismuth-based susceptibility-guided treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
The eradication rate of H. pylori
The investigators define successful eradication as a negative 13C-urea breath test or a negative H. pylori stool antigen test at 4 to 6 weeks after the completion of H. pylori eradication and discontinuation of antibiotics and proton pump inhibitors. The eradication rates are determined by intention-to-treat and per-protocol analyses. The intention-to-treat analysis evaluates all enrolled participants. The per-protocol analysis evaluates those who take >= 80% of the study medications and receive post-treatment 13C-urea breath test or an H. pylori stool antigen test. The successful rate is represented with a percentage (%).
Measured: From enrollment to the end of treatment at 6-8 weeks
Secondary outcomes (2)
Adverse effects
Adverse events are assessed by a physician and a format questionnaire survey after the end of treatment. Serious adverse events are defined as daily activities restricted or participant unable to work. The adverse events include dizziness, skin rash, headache, unpleasant taste/bitter, abdominal pain, nausea, vomiting, diarrhea, constipation, abdominal fullness, glossitis/sore throat, darkened stool, fatigue, anorexia, chest burn, palpitation, and vaginal discharge. All adverse events are classified as none, mild (not restricting daily activities), or serious (restricting daily activities or causing inability to work).
Measured: From enrollment to the end of treatment at 2 weeks
Adherence to medications
Adherence to medications is evaluated by questionnaire surveys after treatment completion. Adherence of medications is categorized as good (≥ 80% medication taken) or poor (< 80% medication taken).
Measured: From enrollment to the end of treatment at 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2024
- Study start1 Jan 2022
- Primary completion31 Mar 2023
- Study completion31 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Helicobacter PyloriStudies of the same condition, open and under way.
- More trials run by National Cheng-Kung University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The multi-resistant H. pylori eradication rates between "bismuth-susceptibility-based regimen" and history "physicians' discretion regimen" are compared.
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cheng-Kung University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Hsiu-Chi Cheng, MD, PhD, Study director, National Cheng-Kung University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06687473
- Sponsor's protocol ID
- B-BR-110-096
- Acronym
- BSUS-1
- Status last verified
- Oct 2024
- First submitted
- 5 Nov 2024
- Last updated
- 13 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 17635369
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Study of Bismuth Salt Effect on the Virulence Factors of Helicobacter Pylori and Its Therapeutic Role for Multiple-resistant Strains
- ClinicalTrials.gov ID
- NCT06687473
- Acronym / sponsor ID
- BSUS-1 / B-BR-110-096
- Keywords
- bismuth, microbial sensitivity tests, Helicobacter pylori, drug resistance, multiple, Virulence Factor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- National Cheng-Kung University HospitalUniversity, hospital or other
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 31 Mar 2023 (actual)
- Study completion
- 31 Mar 2023 (actual)
- First posted
- 13 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The multi-resistant H. pylori eradication rates between "bismuth-susceptibility-based regimen" and history "physicians' discretion regimen" are compared.
| Arm | Type | Receives |
|---|---|---|
| Bismuth-based susceptibility-guided treatment | Experimental | Drug: Bismuth-based susceptibility-guided treatmentParticipants who have triple- or quadruple-drug resistant H. pylori infection are enrolled. Participants receive one of the four regimens based on susceptibility test. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bismuth-based susceptibility-guided treatmentThe 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. | Drug | Bismuth-based susceptibility-guided treatment |
Primary outcome
The eradication rate of H. pylori
Time frame: From enrollment to the end of treatment at 6-8 weeks
The investigators define successful eradication as a negative 13C-urea breath test or a negative H. pylori stool antigen test at 4 to 6 weeks after the completion of H. pylori eradication and discontinuation of antibiotics and proton pump inhibitors. The eradication rates are determined by intention-to-treat and per-protocol analyses. The intention-to-treat analysis evaluates all enrolled participants. The per-protocol analysis evaluates those who take >= 80% of the study medications and receive post-treatment 13C-urea breath test or an H. pylori stool antigen test. The successful rate is represented with a percentage (%).
2 secondary outcomes
Adverse effects
Time frame: From enrollment to the end of treatment at 2 weeks
Adherence to medications
Time frame: From enrollment to the end of treatment at 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2024.
- Background: PubMed 17635369Fischbach 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hsiu-Chi Cheng, MD, PhD study director
National Cheng-Kung University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Bismuth-based susceptibility-guided treatment in people with Helicobacter Pylori and Drug Resistance, Multiple, run by National Cheng-Kung University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The eradication rate of H. pylori (time frame: From enrollment to the end of treatment at 6-8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06687473, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2024.