H Pylori InfectionPhase 4NCT03555526
Genotypic Resistance Guided Therapy for Refractory H. Pylori Infection
A Phase 4 study testing Esomeprazole 40mg, Amoxicillin and metronidazole in people with H Pylori Infection, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- H Pylori Infection
- What is being tested?
- Esomeprazole 40mg, Amoxicillin and metronidazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 1 siteTaiwan
- Study dates
- 15 Dec 2017to 31 Dec 2021
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- H pylori infection failed after at least two eradication therapies
- aged 20 years or greater
- willingness to receive rescue therapy
Who cannot join
- aged less than 20 years
- history of gastric resection surgery
- history of allergy to study drugs
- pregnancy or lactating women
- severe underlying illness, such as end stage renal disease, decompensated liver cirrhosis, or non-curative malignancy
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Jyh-Ming Liou
Taipei, Taiwan, Taiwan, 10002
Jyh-Ming Liou, jyhmingliou@gmail.com
About this study
Official title: Comparison of Genotypic Resistance Guided Versus Susceptibility Testing Guided Therapy for the Third-line Eradication of H. Pylori- a Multicenter Randomized Trial
The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.
Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.
Read more
Methods: This multicenter, open label, parallel group, randomized trial will be conducted since 2017.07.20. Adult (≥20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled. Genotypic and phenotypic resistances will be determined in patients who failed from at least two eradication therapies by polymerase-chain-reaction with direct sequencing and E-test and agar dilution test, respectively. Eligible patients will be randomized into either one of the treatment groups (A) genotypic resistance guided therapy; or (B) susceptibility testing guided therapy.
Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.
Read the detailed description
The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.
Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.
Methods: This multicenter, open label, parallel group, randomized trial will be conducted since 2017.07.20. Adult (≥20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled. Genotypic and phenotypic resistances will be determined in patients who failed from at least two eradication therapies by polymerase-chain-reaction with direct sequencing and E-test and agar dilution test, respectively. Eligible patients will be randomized into either one of the treatment groups (A) genotypic resistance guided therapy; or (B) susceptibility testing guided therapy. Eradication status will be determined by 13C-urea breath test at least 6 weeks after eradication therapy. The stool samples will be collected before, and 2 and 8 weeks and 1 year after eradication therapy to analyze the changes in the antibiotic resistance and microbiota of gut flora. The body weight, waist and hip circumference and serum lipid profile, sugar, and HbA1C levels will also be collected before and 2 weeks, 8 weeks and 1 year after eradication therapy.
Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.
Secondary End Points: the eradication rate according per protocol analysis and the adverse effects
Secondary End Point:
(A) Eradication rate according to per protocol analysis (PP analysis) (B) Frequency of adverse effects (C) The changes in the gut microbiota, antibiotic resistance of the Enterobacteriae, metabolic parameters before and after H. pylori eradication (D) The long term eradication rate and reinfection rate
- Conditions
- H Pylori Infection
- Being tested
- Esomeprazole 40mg, Amoxicillin, metronidazole, Levofloxacin 500mg, Clarithromycin ER
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esomeprazole 40mgDrug
Also called Nexium (Sequential)
Nexium (esomeprazole), 40mg, bid, for 14 days
AmoxicillinDrug
Also called Amoxicillin (Sequential)
amoxicillin, 1000mg, bid, for 7 days (day 1-day 7)
metronidazoleDrug
Also called Flagyl (sequential)
metronidazole, 500mg, bid, for 7 days (day 8-14)
Levofloxacin 500mgDrug
Also called Cravit (sequential)
levofloxacin 250mg, bid, for 7 days (day 8-14)
Clarithromycin ERDrug
Also called Klaricid ER 500 (sequential)
clarithromycin 500mg, bid, for 7 days (day 8-14)
Esomeprazole 40mgDrug
Also called Nexium (bismuth quadruple therapy)
Nexium (esomeprazole), 40mg, bid, for 10 days
Dibismuth trioxideDrug
Also called KCB F.C., bismuth
Dibismuth trioxide，KCB F.C. TABLETS，300mg，qid, for 10 days
metronidazoleDrug
Also called Flagyl (bismuth quadruple)
metronidazole, 500mg, tid, for 10 days (day 1-10)
tetracyclineDrug
Also called tetracycline (bismuth quadruple therapy)
tetracycline 500mg, qid, for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Genotypic resistance guided therapy | Experimental | The regimen will be chosen according to the genotyping of 23S rRNA and gyrase A of H. pylori. In the absence of gyrase A mutation, esomeprazole (Nexium), amoxicillin (Amoxicillin), levofloxacin (Cravit), metronidazole (Flagyl) for 14 days will be given. In the presence of gyrase A mutation but in the absence of 23S rRNA mutation, esomeprazole (Nexium), amoxicillin (Amoxicillin), clarithromycin (Klaricid), metronidazole (Flagyl) for 14 days will be given. In the presence of both gyrase A and 23S rRNA mutation, bismuth quadruple therapy including esomeprazole (Nexium), bismuth (KCB), tetracycline, and metronidazole (Flagyl) for 10 days will be given. Receives: Drug: Esomeprazole 40mg; Drug: Amoxicillin; Drug: metronidazole; Drug: Levofloxacin 500mg; Drug: Clarithromycin ER; Drug: Dibismuth trioxide; Drug: tetracycline |
| Phenotypic resistance guided therapy | Active comparator | The regimen will be chosen according to the susceptibility testing result. In the absence of levofloxacin resistance, esomeprazole (Nexium), amoxicillin (Amoxicillin), levofloxacin (Cravit), metronidazole (Flagyl) for 14 days will be given. In the presence of levofloxacin resistance but in the absence of clarithromycin resistance, esomeprazole (Nexium), amoxicillin (Amoxicillin), clarithromycin (Klaricid), metronidazole (Flagyl) for 14 days will be given. In the presence of both levofloxacin and clarithromycin resistance, bismuth quadruple therapy including esomeprazole (Nexium), bismuth (KCB), tetracycline, and metronidazole (Flagyl) for 10 days will be given. Receives: Drug: Esomeprazole 40mg; Drug: Amoxicillin; Drug: metronidazole; Drug: Levofloxacin 500mg; Drug: Clarithromycin ER; Drug: Dibismuth trioxide; Drug: tetracycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Eradication rate by intention to treat analysis
Measured: 8 weeks
Secondary outcomes (4)
Eradication rate by per protocol analysis
Measured: 8 weeks
frequency of adverse effects during eradication therapy
Measured: 2 weeks
changes of fecal microbiota
changes of fecal microbiota before and after erdication therapy
Measured: 1 year
reinfection rate
reinfection rate 1 year after eradication therapy
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2018
- Study start15 Dec 2017
- Primary completion1 Sep 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
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 H Pylori InfectionStudies of the same condition, open and under way.
- More trials run by National Taiwan 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 320 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jyh-Ming Liou, MD, PhD, Principal investigator, National Taiwan University Hospital (recruiting)Yen-Nien Chen, MD, Principal investigator, National Taiwan University Hospital Hsin-Chu BranchYu Jen Fang, MD, Principal investigator, National Taiwan University Hospital, Yun-Lin Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03555526
- Sponsor's protocol ID
- 201706037MINC
- Status last verified
- Dec 2017
- First submitted
- 14 Dec 2017
- Last updated
- 13 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Chen MJ, Chen PY, Fang YJ, Bair MJ, Chen CC, Chen CC, Yang TH, Lee JY, Yu CC, Kuo CC, Chiu MC, Chou CK, Chen CY, Hu WH, Tsai MH, Hsu YC, Shun CT, Luo JC, Lin JT, El-Omar EM, Wu MS, Liou JM; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Molecular testing-guided therapy versus susceptibility testing-guided therapy in first-line and third-line Helicobacter pylori eradication: two multicentre, open-label, randomised controlled, non-inferiority trials. Lancet Gastroenterol Hepatol. 2023 Jul;8(7):623-634. doi: 10.1016/S2468-1253(23)00097-3. Epub 2023 May 10.
PubMed 37178702
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Genotypic Resistance Guided Versus Susceptibility Testing Guided Therapy for the Third-line Eradication of H. Pylori- a Multicenter Randomized Trial
- ClinicalTrials.gov ID
- NCT03555526
- Acronym / sponsor ID
- 201706037MINC
- Conditions
- H Pylori Infection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 320 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 15 Dec 2017 (actual)
- Primary completion
- 1 Sep 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 13 Jun 2018 (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 inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.
Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.
Methods: This multicenter, open label, parallel group, randomized trial will be conducted since 2017.07.20. Adult (≥20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled. Genotypic and phenotypic resistances will be determined in patients who failed from at least two eradication therapies by polymerase-chain-reaction with direct sequencing and E-test and agar dilution test, respectively. Eligible patients will be randomized into either one of the treatment groups (A) genotypic resistance guided therapy; or (B) susceptibility testing guided therapy.
Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.
Detailed description
The inviestigators aimed to compare the efficacy of genotypic resistance guided versus susceptibility testing guided therapy in the third line treatment for refractory H. pylori infection.
Hypothesis:The investigators hypothesized that genotypic resistance guided sequential therapy is non-inferior to empiric therapy in the third line treatment for refractory H. pylori infection.
Methods: This multicenter, open label, parallel group, randomized trial will be conducted since 2017.07.20. Adult (≥20 years old) patients who failed from at least two eradication therapies for H. pylori infection will be enrolled. Genotypic and phenotypic resistances will be determined in patients who failed from at least two eradication therapies by polymerase-chain-reaction with direct sequencing and E-test and agar dilution test, respectively. Eligible patients will be randomized into either one of the treatment groups (A) genotypic resistance guided therapy; or (B) susceptibility testing guided therapy. Eradication status will be determined by 13C-urea breath test at least 6 weeks after eradication therapy. The stool samples will be collected before, and 2 and 8 weeks and 1 year after eradication therapy to analyze the changes in the antibiotic resistance and microbiota of gut flora. The body weight, waist and hip circumference and serum lipid profile, sugar, and HbA1C levels will also be collected before and 2 weeks, 8 weeks and 1 year after eradication therapy.
Outcome Measurement The primary outcome is the eradication rate in the third line treatment (genotypic versus susceptibility testing guided therapy) according to intention-to-treat (ITT) analysis.
Secondary End Points: the eradication rate according per protocol analysis and the adverse effects
Secondary End Point:
(A) Eradication rate according to per protocol analysis (PP analysis) (B) Frequency of adverse effects (C) The changes in the gut microbiota, antibiotic resistance of the Enterobacteriae, metabolic parameters before and after H. pylori eradication (D) The long term eradication rate and reinfection rate
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Genotypic resistance guided therapy | Experimental | Drug: Esomeprazole 40mg, Drug: Amoxicillin, Drug: metronidazole, Drug: Levofloxacin 500mg, Drug: Clarithromycin ER, Drug: Dibismuth trioxide, Drug: tetracyclineThe regimen will be chosen according to the genotyping of 23S rRNA and gyrase A of H. pylori. In the absence of gyrase A mutation, esomeprazole (Nexium), amoxicillin (Amoxicillin), levofloxacin (Cravit), metronidazole (Flagyl) for 14 days will be given. In the presence of gyrase A mutation but in the absence of 23S rRNA mutation, esomeprazole (Nexium), amoxicillin (Amoxicillin), clarithromycin (Klaricid), metronidazole (Flagyl) for 14 days will be given. In the presence of both gyrase A and 23S rRNA mutation, bismuth quadruple therapy including esomeprazole (Nexium), bismuth (KCB), tetracycline, and metronidazole (Flagyl) for 10 days will be given. |
| Phenotypic resistance guided therapy | Active comparator | Drug: Esomeprazole 40mg, Drug: Amoxicillin, Drug: metronidazole, Drug: Levofloxacin 500mg, Drug: Clarithromycin ER, Drug: Dibismuth trioxide, Drug: tetracyclineThe regimen will be chosen according to the susceptibility testing result. In the absence of levofloxacin resistance, esomeprazole (Nexium), amoxicillin (Amoxicillin), levofloxacin (Cravit), metronidazole (Flagyl) for 14 days will be given. In the presence of levofloxacin resistance but in the absence of clarithromycin resistance, esomeprazole (Nexium), amoxicillin (Amoxicillin), clarithromycin (Klaricid), metronidazole (Flagyl) for 14 days will be given. In the presence of both levofloxacin and clarithromycin resistance, bismuth quadruple therapy including esomeprazole (Nexium), bismuth (KCB), tetracycline, and metronidazole (Flagyl) for 10 days will be given. |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- H pylori infection failed after at least two eradication therapies
- aged 20 years or greater
- willingness to receive rescue therapy
Key exclusion criteria (5 listed)
- aged less than 20 years
- history of gastric resection surgery
- history of allergy to study drugs
- pregnancy or lactating women
- severe underlying illness, such as end stage renal disease, decompensated liver cirrhosis, or non-curative malignancy
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 |
|---|---|---|
| Esomeprazole 40mgAlso: Nexium (Sequential)Nexium (esomeprazole), 40mg, bid, for 14 days | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| AmoxicillinAlso: Amoxicillin (Sequential)amoxicillin, 1000mg, bid, for 7 days (day 1-day 7) | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| metronidazoleAlso: Flagyl (sequential)metronidazole, 500mg, bid, for 7 days (day 8-14) | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| Levofloxacin 500mgAlso: Cravit (sequential)levofloxacin 250mg, bid, for 7 days (day 8-14) | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| Clarithromycin ERAlso: Klaricid ER 500 (sequential)clarithromycin 500mg, bid, for 7 days (day 8-14) | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| Esomeprazole 40mgAlso: Nexium (bismuth quadruple therapy)Nexium (esomeprazole), 40mg, bid, for 10 days | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| Dibismuth trioxideAlso: KCB F.C., bismuthDibismuth trioxide，KCB F.C. TABLETS，300mg，qid, for 10 days | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| metronidazoleAlso: Flagyl (bismuth quadruple)metronidazole, 500mg, tid, for 10 days (day 1-10) | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
| tetracyclineAlso: tetracycline (bismuth quadruple therapy)tetracycline 500mg, qid, for 10 days | Drug | Genotypic resistance guided therapy, Phenotypic resistance guided therapy |
Primary outcome
Eradication rate by intention to treat analysis
Time frame: 8 weeks
4 secondary outcomes
Eradication rate by per protocol analysis
Time frame: 8 weeks
frequency of adverse effects during eradication therapy
Time frame: 2 weeks
changes of fecal microbiota
Time frame: 1 year
reinfection rate
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2018.
- Derived from this study: PubMed 37178702Chen MJ, Chen PY, Fang YJ, Bair MJ, Chen CC, Chen CC, Yang TH, Lee JY, Yu CC, Kuo CC, Chiu MC, Chou CK, Chen CY, Hu WH, Tsai MH, Hsu YC, Shun CT, Luo JC, Lin JT, El-Omar EM, Wu MS, Liou JM; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Molecular testing-guided therapy versus susceptibility testing-guided therapy in first-line and third-line Helicobacter pylori eradication: two multicentre, open-label, randomised controlled, non-inferiority trials. Lancet Gastroenterol Hepatol. 2023 Jul;8(7):623-634. doi: 10.1016/S2468-1253(23)00097-3. Epub 2023 May 10.
- 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.
Jyh-Ming Liou, MD, PhD principal investigator
National Taiwan University Hospital (recruiting)
Yen-Nien Chen, MD principal investigator
National Taiwan University Hospital Hsin-Chu Branch
Yu Jen Fang, MD principal investigator
National Taiwan University Hospital, Yun-Lin Branch
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 Esomeprazole 40mg, Amoxicillin and metronidazole in people with H Pylori Infection, run by National Taiwan 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 5 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: status not confirmed, as of the sponsor's last update on 13 Jun 2018. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jyh-Ming Liou, MD, PhD (886972651883, jyhmingliou@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Eradication rate by intention to treat analysis (time frame: 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 NCT03555526, 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 Jun 2018.