Sequential Versus Quadruple Therapy in the Second-line Treatment

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: Esomeprazole (S14)
* Drug: Esomeprazole (BQ10)
* Drug: Amoxicillin (ST14)
* Drug: Clarithromycin (ST14)
* Drug: Metronidazole (ST14)
* Drug: dibismuth trioxide 120mg (BQ10)
* Drug: Metronidazole (BQ10)
* Drug: tetracycline (BQ10)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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, pregnant or lactating women, severe concurrent disease, or Unwilling to accept random assignment of subjects.

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequential therapy for 14 days<br>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 | Drug: Esomeprazole (S14)<br>* Nexium, esomeprazole 40mg bid, 14 days<br>* Other names: Nexium;Drug: Amoxicillin (ST14)<br>* Day 1-7 amoxicillin (Brand name: Amoxicillin Capsule) 1000mg bid for 7 days<br>* Other names: amoxicillin capsule;Drug: Clarithromycin (ST14)<br>* Klaricid-XL, clarithromycin, 500mg, bid, for 7 days, (day 8-14)<br>* Other names: Klaricid-XL 500mg;Drug: Metronidazole (ST14)<br>* Flagyl, metronidazole, 500mg bid, for 7 days (day 8-14)<br>* Other names: Flagyl;|
| Active Comparator: bismuth quadruple therapy for 10 days<br>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 | Drug: Esomeprazole (BQ10)<br>* Nexium, esomeprazole, 40mg bid for 10 days<br>* Other names: Nexium (BQ10);Drug: dibismuth trioxide 120mg (BQ10)<br>* KCB F.C. TABLETS, dibismuth trioxide 120mg qid for 10 days<br>* Other names: KCB F.C. TABLETS;Drug: Metronidazole (BQ10)<br>* Flagyl, metronidazole 500mg tid for 10 days<br>* Other names: Flagyl;Drug: tetracycline (BQ10)<br>* Tetracycline (Brand name: Tetracycline Capsule ) 500mg qid for 10 days<br>* Other names: Tetracycline Capsule;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | 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 | 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. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Efficacy, Self