Helicobacter Pylori InfectionPhase 4NCT03208426
Sequential Versus Quadruple Therapy in the Second-line Treatment
A Phase 4 study testing Esomeprazole (S14), Esomeprazole (BQ10) and Amoxicillin (ST14) in people with Helicobacter Pylori Infection, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
Objectives: A recent randomized trial showed that 14-day sequential therapy containing high dose proton pump inhibitor was higher than 95% in the first line treatment. However, whether the 14-day sequential therapy is more effective than 10-day bismuth quadruple therapy remains unknown. Read more about this study
- Who is it for?
- Ages 20 years and olderHealthy volunteers can take part
- Conditions the study is for
- Helicobacter Pylori Infection
- What is being tested?
- Esomeprazole (S14), Esomeprazole (BQ10) and Amoxicillin (ST14)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Oct 2017to 31 Dec 2020
- 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 infected patients who fail from first line standard triple therapy with clarithromycin, amoxicillin, and a proton pump inhibitor will be eligible in this study.
Who cannot join
- Patients will be excluded from the study if any one of the following criteria was present:
- children and teenagers aged less than 20 years,
- history of gastrectomy,
- gastric malignancy, including adenocarcinoma and lymphoma,
- previous allergic reaction to antibiotics (bismuth, metronidazole, levofloxacin, tetracycline) and PPI (esomeprazole),
- contraindication to treatment drugs,
Show all 9Show fewer
- pregnant or lactating women,
- severe concurrent disease, or
- Unwilling to accept random assignment of subjects.
Trial locations and contacts
1 site in 1 country.
Taiwan1 site, 1 recruiting
- Recruiting
Jyh-Ming Liou
Taipei, Taiwan, 10002
Jyh-Ming Liou, jyhmingliou@gmail.com
Ming-Shiang Wu
About this study
Official title: Comparison of the Efficacy of 14-day Sequential Therapy and 10-day Bismuth Quadruple Therapy in the Second Line Therapy for Helicobacter Pylori Infection: A Multi-center Randomized Trial
Objectives: A recent randomized trial showed that 14-day sequential therapy containing high dose proton pump inhibitor was higher than 95% in the first line treatment. However, whether the 14-day sequential therapy is more effective than 10-day bismuth quadruple therapy remains unknown. Therefore, the investigators aimed to compare the eradication rates and long term re-infection rates of sequential therapy for 14 days versus bismuth quadruple therapy for 10 days in the second line treatment.
Read the detailed description
This will be a multi-center, open labeled, randomized comparative trial Patients: 240 patients with H. pylori infection who failed after first-line therapy will be eligible
Interventions: eligible patients will be randomized into one of the two groups Group (A): sequential therapy for 14 days (S14)
D1-D7: (esomeprazole 40mg bid + amoxicillin 1000mg bid) for 7 days
D8-D14: (esomeprazole 40mg bid + clarithromycin 500mg bid + metronidazole 500mg bid) for another 7 days
Group (B): bismuth quadruple therapy for 10 days (Q10)
D1-D10: (esomeprazole 40mg bid + dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days
Primary End Point: Eradication rate in the second line treatment according to intention to treat (ITT) analysis in the two treatment groups
- Conditions
- Helicobacter Pylori Infection
- Being tested
- Esomeprazole (S14), Esomeprazole (BQ10), Amoxicillin (ST14), Clarithromycin (ST14), Metronidazole (ST14)
- Keywords
- Efficacy, Self
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Esomeprazole (S14)Drug
Also called Nexium
Nexium, esomeprazole 40mg bid, 14 days
Esomeprazole (BQ10)Drug
Also called Nexium (BQ10)
Nexium, esomeprazole, 40mg bid for 10 days
Amoxicillin (ST14)Drug
Also called amoxicillin capsule
Day 1-7 amoxicillin (Brand name: Amoxicillin Capsule) 1000mg bid for 7 days
Clarithromycin (ST14)Drug
Also called Klaricid-XL 500mg
Klaricid-XL, clarithromycin, 500mg, bid, for 7 days, (day 8-14)
Metronidazole (ST14)Drug
Also called Flagyl
Flagyl, metronidazole, 500mg bid, for 7 days (day 8-14)
dibismuth trioxide 120mg (BQ10)Drug
Also called KCB F.C. TABLETS
KCB F.C. TABLETS, dibismuth trioxide 120mg qid for 10 days
Metronidazole (BQ10)Drug
Also called Flagyl
Flagyl, metronidazole 500mg tid for 10 days
tetracycline (BQ10)Drug
Also called Tetracycline Capsule
Tetracycline (Brand name: Tetracycline Capsule ) 500mg qid for 10 days
| Study group | Role | What they receive |
|---|---|---|
| Sequential therapy for 14 days | Experimental | Sequential therapy for 14 days (experimental) D1-D7: (Nexium, esomeprazole 40mg bid + amoxicillin (Brand name: Amoxicillin Capsule) 1000mg bid) for 7 days D8-D14: (Nexium, esomeprazole 40mg bid + Klaricid XL, clarithromycin 500mg bid + Flagyl, metronidazole 500mg bid) for another 7 days Receives: Drug: Esomeprazole (S14); Drug: Amoxicillin (ST14); Drug: Clarithromycin (ST14); Drug: Metronidazole (ST14) |
| bismuth quadruple therapy for 10 days | Active comparator | Bismuth quadruple therapy for 10 days (active comparator) D1-D10: (Nexium, esomeprazole 40mg bid + KCB F.C. TABLETS, dibismuth trioxide 120mg qid + Flagyl, metronidazole 500mg tid + tetracycline (Brand name: Tetracycline Capsule ) 500mg qid) for 10 days Receives: Drug: Esomeprazole (BQ10); Drug: dibismuth trioxide 120mg (BQ10); Drug: Metronidazole (BQ10); Drug: tetracycline (BQ10) |
What is being measured
The primary outcome is the main question the study is designed to answer.
eradication rate in the second-line treatment according to intention to treat (ITT) analysis
Urea breath test will be performed at least 6 weeks after the end of eradication therapy. Successful eradication of H. pylori will be defined as a negative 13C-UBT result. A positive 13C-UBT test will be defined as a delta value of 4 units or greater. All subjects will be asked to stop PPI and H2-blocker for at least two weeks before 13C-UBT.
Measured: 6 weeks
Secondary outcomes (4)
Incidence of adverse effects in the first line therapy in the two treatment groups
At enrollment, the patients will be informed of the common side effects from the studied drugs and they will be asked to record these symptoms during treatment. A standardized interview and questionnaire will be used to assess the adverse events
Measured: 2 weeks
Eradication rates in the second line treatment according to per protocol (PP) analysis
Urea breath test will be performed at least 6 weeks after the end of eradication therapy. Patients not follow the protocol will be excluded for PP analysis.
Measured: 6 weeks
Changes of gut microbiota in the two treatment groups
the stool specimens before, 2weeks after, 8 weeks after, and 1 year after the treatment will be collected for gut microbiota analysis
Measured: 2 weeks, 8 weeks, and 1 year
Re-infection rate one year after eradication therapy
Urea breath test will be performed 1 year after the end of 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 posted5 Jul 2017
- Study start1 Oct 2017
- Primary completion31 Dec 2019 (estimated)
- Study completion31 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Helicobacter 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
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 240 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, Study chair, National Taiwan University HospitalYu-Jen Fang, MD, Principal investigator, National Taiwan University Hospital, Yun-Lin Branch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03208426
- Sponsor's protocol ID
- 201611053MINA
- Status last verified
- Jun 2018
- First submitted
- 21 May 2017
- Last updated
- 4 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Liou JM, Fang YJ, Chen CC, Bair MJ, Chang CY, Lee YC, Chen MJ, Chen CC, Tseng CH, Hsu YC, Lee JY, Yang TH, Luo JC, Chang CC, Chen CY, Chen PY, Shun CT, Hsu WF, Hu WH, Chen YN, Sheu BS, Lin JT, Wu JY, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2016 Nov 12;388(10058):2355-2365. doi: 10.1016/S0140-6736(16)31409-X. Epub 2016 Oct 18.
PubMed 27769562Liou JM, Chen CC, Chen MJ, Chen CC, Chang CY, Fang YJ, Lee JY, Hsu SJ, Luo JC, Chang WH, Hsu YC, Tseng CH, Tseng PH, Wang HP, Yang UC, Shun CT, Lin JT, Lee YC, Wu MS; Taiwan Helicobacter Consortium. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013 Jan 19;381(9862):205-13. doi: 10.1016/S0140-6736(12)61579-7. Epub 2012 Nov 16.
PubMed 23158886Yang TH, Lee JY, Yu JJ, Kuo CC, Chiu MC, Hu WH, Tsai MH, Chen PY, Chou CK, Chen CY, Bair MJ, Cheng HC, Chen MJ, Chen CC, Wu MS, Liou JM, Fang YJ; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Comparison of the efficacy of 14-day sequential therapy and 10-day bismuth quadruple therapy in the second line therapy for Helicobacter pylori infection- A multi-center randomized trial. J Formos Med Assoc. 2026 Aug 13:S0929-6646(26)00803-X. doi: 10.1016/j.jfma.2026.08.015. Online ahead of print.
PubMed 42595603
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Efficacy of 14-day Sequential Therapy and 10-day Bismuth Quadruple Therapy in the Second Line Therapy for Helicobacter Pylori Infection: A Multi-center Randomized Trial
- ClinicalTrials.gov ID
- NCT03208426
- Acronym / sponsor ID
- 201611053MINA
- Conditions
- Helicobacter Pylori Infection
- Keywords
- Efficacy, Self
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 31 Dec 2019 (estimated)
- Study completion
- 31 Dec 2020 (estimated)
- First posted
- 5 Jul 2017 (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.
Objectives: A recent randomized trial showed that 14-day sequential therapy containing high dose proton pump inhibitor was higher than 95% in the first line treatment. However, whether the 14-day sequential therapy is more effective than 10-day bismuth quadruple therapy remains unknown. Therefore, the investigators aimed to compare the eradication rates and long term re-infection rates of sequential therapy for 14 days versus bismuth quadruple therapy for 10 days in the second line treatment.
Detailed description
This will be a multi-center, open labeled, randomized comparative trial Patients: 240 patients with H. pylori infection who failed after first-line therapy will be eligible
Interventions: eligible patients will be randomized into one of the two groups Group (A): sequential therapy for 14 days (S14)
D1-D7: (esomeprazole 40mg bid + amoxicillin 1000mg bid) for 7 days
D8-D14: (esomeprazole 40mg bid + clarithromycin 500mg bid + metronidazole 500mg bid) for another 7 days
Group (B): bismuth quadruple therapy for 10 days (Q10)
D1-D10: (esomeprazole 40mg bid + dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days
Primary End Point: Eradication rate in the second line treatment according to intention to treat (ITT) analysis in the two treatment groups
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequential therapy for 14 days | Experimental | Drug: Esomeprazole (S14), Drug: Amoxicillin (ST14), Drug: Clarithromycin (ST14), Drug: Metronidazole (ST14)Sequential therapy for 14 days (experimental) D1-D7: (Nexium, esomeprazole 40mg bid + amoxicillin (Brand name: Amoxicillin Capsule) 1000mg bid) for 7 days D8-D14: (Nexium, esomeprazole 40mg bid + Klaricid XL, clarithromycin 500mg bid + Flagyl, metronidazole 500mg bid) for another 7 days |
| bismuth quadruple therapy for 10 days | Active comparator | Drug: Esomeprazole (BQ10), Drug: dibismuth trioxide 120mg (BQ10), Drug: Metronidazole (BQ10), Drug: tetracycline (BQ10)Bismuth quadruple therapy for 10 days (active comparator) D1-D10: (Nexium, esomeprazole 40mg bid + KCB F.C. TABLETS, dibismuth trioxide 120mg qid + Flagyl, metronidazole 500mg tid + tetracycline (Brand name: Tetracycline Capsule ) 500mg qid) for 10 days |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- H. pylori infected patients who fail from first line standard triple therapy with clarithromycin, amoxicillin, and a proton pump inhibitor will be eligible in this study.
Key exclusion criteria (9 listed)
- Patients will be excluded from the study if any one of the following criteria was present:
- children and teenagers aged less than 20 years,
- history of gastrectomy,
- gastric malignancy, including adenocarcinoma and lymphoma,
- previous allergic reaction to antibiotics (bismuth, metronidazole, levofloxacin, tetracycline) and PPI (esomeprazole),
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 (S14)Also: NexiumNexium, esomeprazole 40mg bid, 14 days | Drug | Sequential therapy for 14 days |
| Esomeprazole (BQ10)Also: Nexium (BQ10)Nexium, esomeprazole, 40mg bid for 10 days | Drug | bismuth quadruple therapy for 10 days |
| Amoxicillin (ST14)Also: amoxicillin capsuleDay 1-7 amoxicillin (Brand name: Amoxicillin Capsule) 1000mg bid for 7 days | Drug | Sequential therapy for 14 days |
| Clarithromycin (ST14)Also: Klaricid-XL 500mgKlaricid-XL, clarithromycin, 500mg, bid, for 7 days, (day 8-14) | Drug | Sequential therapy for 14 days |
| Metronidazole (ST14)Also: FlagylFlagyl, metronidazole, 500mg bid, for 7 days (day 8-14) | Drug | Sequential therapy for 14 days |
| dibismuth trioxide 120mg (BQ10)Also: KCB F.C. TABLETSKCB F.C. TABLETS, dibismuth trioxide 120mg qid for 10 days | Drug | bismuth quadruple therapy for 10 days |
| Metronidazole (BQ10)Also: FlagylFlagyl, metronidazole 500mg tid for 10 days | Drug | bismuth quadruple therapy for 10 days |
| tetracycline (BQ10)Also: Tetracycline CapsuleTetracycline (Brand name: Tetracycline Capsule ) 500mg qid for 10 days | Drug | bismuth quadruple therapy for 10 days |
Primary outcome
eradication rate in the second-line treatment according to intention to treat (ITT) analysis
Time frame: 6 weeks
Urea breath test will be performed at least 6 weeks after the end of eradication therapy. Successful eradication of H. pylori will be defined as a negative 13C-UBT result. A positive 13C-UBT test will be defined as a delta value of 4 units or greater. All subjects will be asked to stop PPI and H2-blocker for at least two weeks before 13C-UBT.
4 secondary outcomes
Incidence of adverse effects in the first line therapy in the two treatment groups
Time frame: 2 weeks
Eradication rates in the second line treatment according to per protocol (PP) analysis
Time frame: 6 weeks
Changes of gut microbiota in the two treatment groups
Time frame: 2 weeks, 8 weeks, and 1 year
Re-infection rate one year after eradication therapy
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 4 Jun 2018.
- Results publication: PubMed 27769562Liou JM, Fang YJ, Chen CC, Bair MJ, Chang CY, Lee YC, Chen MJ, Chen CC, Tseng CH, Hsu YC, Lee JY, Yang TH, Luo JC, Chang CC, Chen CY, Chen PY, Shun CT, Hsu WF, Hu WH, Chen YN, Sheu BS, Lin JT, Wu JY, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Concomitant, bismuth quadruple, and 14-day triple therapy in the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2016 Nov 12;388(10058):2355-2365. doi: 10.1016/S0140-6736(16)31409-X. Epub 2016 Oct 18.
- Results publication: PubMed 23158886Liou JM, Chen CC, Chen MJ, Chen CC, Chang CY, Fang YJ, Lee JY, Hsu SJ, Luo JC, Chang WH, Hsu YC, Tseng CH, Tseng PH, Wang HP, Yang UC, Shun CT, Lin JT, Lee YC, Wu MS; Taiwan Helicobacter Consortium. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet. 2013 Jan 19;381(9862):205-13. doi: 10.1016/S0140-6736(12)61579-7. Epub 2012 Nov 16.
- Derived from this study: PubMed 42595603Yang TH, Lee JY, Yu JJ, Kuo CC, Chiu MC, Hu WH, Tsai MH, Chen PY, Chou CK, Chen CY, Bair MJ, Cheng HC, Chen MJ, Chen CC, Wu MS, Liou JM, Fang YJ; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Comparison of the efficacy of 14-day sequential therapy and 10-day bismuth quadruple therapy in the second line therapy for Helicobacter pylori infection- A multi-center randomized trial. J Formos Med Assoc. 2026 Aug 13:S0929-6646(26)00803-X. doi: 10.1016/j.jfma.2026.08.015. Online ahead of print.
- 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 study chair
National Taiwan University Hospital
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 (S14), Esomeprazole (BQ10) and Amoxicillin (ST14) in people with Helicobacter 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 1 inclusion and 9 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 4 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 (886-2-23123456 ext. 63541, 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 in the second-line treatment according to intention to treat (ITT) analysis (time frame: 6 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 NCT03208426, which also lists 3 linked publications.
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 4 Jun 2018.