Comparison of the Levofloxacin Sequential Therapy and Quadruple Therapy in Second Line Treatment for HP

Study Overview
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Brief Summary
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Objectives: Eradication of H. pylori infection could reduce the occurence or recurrence of gastric cancer and peptic ulcer diseases. However, it was estimated that 15-20% of patients would fail from first line standard eradication therapy and need second line rescue therapy. About 15-30% of patient would fail from second line therapy. Bismuth quadruple therapy and triple therapy containing levofloxacin are currently the recommended rescue therapies in the second line and third line treatment. Recently, our pilot study showed that modified sequential therapy containing levofloxacin achieved high eradication rate (95%) in the second line therapy. The regimen includes a PPI plus amoxicillin for 5-7 days, followed by a PPI plus levofloxacin and metronidazole for another 5-7 days. However, whether this modified sequential therapy containing levofloxacin is more effective than bismuth quadruple therapy in the second line and third line treatment remains unknown. Besides, the impact of these regimens on the antibiotic resistance , microbiota of gut flora, and metabolic factors remains unknown. Aims: Therefore, the investigators aimed to compare the eradication rates and long term re-infection rates of sequential therapy containing levofloxacin for 14 days versus bismuth quadruple therapy for 10 days in the second line and third line treatment assess the impact of antibiotic resistance and CYP2C19 polymorphism on the eradication rate of these regimens assess the impact of these eradication regimens on the antibiotic resistance and microbiota of the gut flora assess the impact of eradication therapy on the metabolic factors

Detailed Description
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Methods: This will be a multi-center, open labeled, randomized comparative trial with cross-over design Patients: Participants with refractory H. pylori infection after one eradication therapy Testing for H. pylori infection Before Second Line Treatment : Any two positive of CLO test, histology, and culture or a positive UBT will be considered as H. pylori infected After Second Line Treatment: C13-UBT will be used to assess the existence of H. pylori 6-8 weeks after first line therapy. Long term reinfection: C13-UBT will be used to assess the recurrence of H. pylori 1 year after eradication therapy Interventions: Second line therapy: eligible patients will be randomized into one of the two groups Group (A): sequential therapy containing levofloxacin for 14 days (EAML) D1-D7: (esomeprazole 40mg bid + amoxicillin 1gm bid) for 7 days D8-D14: (esomeprazole 40mg bid + levofloxacin 250mg bid + metronidazole 500mg bid) for another 7 days Group (B): bismuth quadruple therapy for 10 days (BQ) D1-D10: (esomeprazole 40mg bid + Dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days Third line therapy: patients who fail from second line treatment will be rescue with the following treatment Group (A) Patient who fail from levofloxacin sequential therapy will be retreated with bismuth quadruple therapy for 10 days D1-D10: (esomeprazole 40mg bid + Dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days Group (B) Patient who fail from bismuth quadruple therapy will be retreated with levofloxacin sequential therapy for 14days D1-D7: (esomeprazole 40mg bid + amoxicillin 1gm bid) for 7 days D8-D14: (esomeprazole 40mg bid + levofloxacin 250mg bid + metronidazole 500mg bid) for another 7 days Outcome Measurement: Primary End Point: Eradication rate in the second line according to intention to treat (ITT) and per-protocol (PP) analysis in the two treatment groups

Official Title
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Comparison of the Efficacy of Levofloxacin-based Sequential Therapy and Bismuth Quadruple Therapy in the Second Line and Third Line Therapy for Helicobacter Pylori Infection- A Multi-center Randomized Trial

Conditions
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Helicobacter

Intervention / Treatment
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* Drug: Levofloxacin based sequential therapy
* Drug: bismuth quadruple therapy for 10 days (BQ)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. H. pylori infected patients who failed from first line standard triple therapy with clarithromycin, amoxicillin, and a proton pump inhibitor were eligible in this study Exclusion Criteria: 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Levofloxacin based sequential therapy<br>Levofloxacin based sequential therapy : sequential therapy containing levofloxacin for 14 days D1-D7: (esomeprazole 40mg bid + amoxicillin 1gm bid) for 7 days D8-D14: (esomeprazole 40mg bid + levofloxacin 250mg bid + metronidazole 500mg bid) for another 7 days | Drug: Levofloxacin based sequential therapy<br>* D1-D7: (esomeprazole 40mg bid + amoxicillin 1gm bid) for 7 days D8-D14: (esomeprazole 40mg bid + levofloxacin 250mg bid + metronidazole 500mg bid) for another 7 days<br>|
| Active Comparator: bismuth quadruple therapy (BQ)<br>bismuth quadruple therapy for 10 days (BQ) D1-D10: (esomeprazole 40mg bid + Dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days | Drug: bismuth quadruple therapy for 10 days (BQ)<br>* D1-D10: (esomeprazole 40mg bid + Dibismuth trioxide 120mg qid + metronidazole 500mg tid + tetracycline 500mg qid) for 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eradication rate after second line eradication therapy according to ITT analysis | The eradication status will be determined by urea breath test (UBT) at least 6 weeks after completion of the treatment. The delta value of UBT of 4 or less will be defined as negative and successful eradication. | 6 weeks after completion of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse effects during eradication therapy | adverse effects will be assessed by questionnaire | during treatment (2 weeks) | 
| Long term eradication rate 1 year after eradication therapy | Long term eradication rates will be determined by UBT at 1 year after eradication therapy. | 1 year after treatment | 
| changes of gut microbiota before and after eradication therapy | Fecal DNA will be extracted and 16S rRNA sequencing will be done. The changes in the alpha and beta diversity and the compositions of gut microbiota before and after HP eradication will be assessed. | 1 year | 

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