High Dose Amoxicillin Versus Tetracycline as Second-line Treatment of Resistant Helicobacter Pylori Infection

Study Overview
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Brief Summary
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No trial has examined the the efficacy of high dose amoxicillin based quadruple therapy as second-line treatment for Helicobacter pylori infection. The study aims to compare the effectiveness and safety of 14-day high dose amoxicillin-based quadruple regiment with classical quadruple regiment for rescue eradication of Helicobacter pylori.

Detailed Description
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Helicobacter pylori is the most successful human pathogen infecting an estimated 50% of the global population, and is associated with a spectrum of disease states, including chronic gastritis, duodenal and gastric ulcer, gastric adenocarcinoma, and gastric mucosa-associated lymphoid tissue lymphoma (MALToma). Most Consensus Conferences and Clinical Guidelines recommend the prescription of a triple therapy including a proton pump inhibitor (PPI) and clarithromycin with either amoxicillin or metronidazole, as first-line treatment. However, the effectiveness of these triple-therapy regimens seems to have diminished over time, largely as a result of emerging resistance of the organism to clarithromycin. Avoiding problems due to antibiotic resistance has become an important issue when deciding a second-line rescue therapy for H. pylori infection Bismuth-containing quadruple therapies have been used widely in second-line therapy of H. pylori infection, and are recommended by the Maastricht IV Consensus Conference report. Quadruple therapy can achieve a high rate of eradication success as a second-line treatment. A meta-analysis of quadruple therapy showed that metronidazole resistance had limited effect on the outcome when adequate dosages and durations are used. This meta-analysis also showed that compliance with quadruple therapy is high. Classical bismuth-based quadruple therapy consists of a PPI, bismuth, tetracycline and metronidazole. This regiment meets the proposed criteria for a second-line treatment: it does not contain the key antibiotic of the original regimen (clarithromycin), the treatment is not affected by clarithromycin resistance, metronidazole resistance in vitro does not affect the outcome of quadruple therapy significantly, compliance with the regimen is high and the regimen is effective in most parts of the world. But this regiment has high rate of side effects because of tetracycline. Amoxicillin has low resistance rate as well as low percentage of side effects. The replacement of tetracycline by high dose amoxicillin in classical bismuth-containing quadruple therapy may be a better choice. Therefore, we will do a randomized trial to compare the eradication rate of 14-day high dose amoxicillin and metronidazole based bismuth-containing quadruple therapy with classical quadruple therapy for second-line Helicobacter pylori treatment.

Official Title
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Prospective, Randomized Controlled Trial Comparing High Dose Amoxicillin Versus Tetracycline Based Quadruple Therapy as Second-line Treatment for Resistant Helicobacter Pylori Infection

Conditions
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Helicobacter Pylori Treatment Failure

Intervention / Treatment
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* Drug: Lansoprazole
* Drug: Bismuth Potassium Citrate
* Drug: Metronidazole
* Drug: Amoxicillin
* Drug: Tetracycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: all patients had failed H.pylori therapies including clarithromycin, metronidazole and/or amoxicillin (if not allergic) before indication of rescue H pylori eradication treatment Ability and willingness to participate in the study and to sign and give informed consent Exclusion Criteria: patients less than 18 years old previous gastric surgery pregnancy or lactation major systemic diseases, administration of antibiotics, bismuth, antisecretory drugs in the preceding 8 weeks allergy to any one of the medication used in the quadruple regimens.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Dose Amoxicillin<br>High dose amoxicillin/metronidazole-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Amoxicillin 1000mg tid, Metronidazole 400mg qid | Drug: Lansoprazole<br>* antisecretory drug of each quadruple therapy<br>* Other names: proton pump inhibitor;Drug: Bismuth Potassium Citrate<br>* one component of each quadruple therapy<br>* Other names: Bismuth;Drug: Metronidazole<br>* antibiotic of each quadruple therapy<br>* Other names: antibiotic;Drug: Amoxicillin<br>* antibiotic of high dose amoxicillin based quadruple therapy<br>* Other names: antibiotic;|
| Active Comparator: Tetracycline<br>Classical quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Tetracycline 500mg qid, Metronidazole 400mg qid | Drug: Lansoprazole<br>* antisecretory drug of each quadruple therapy<br>* Other names: proton pump inhibitor;Drug: Bismuth Potassium Citrate<br>* one component of each quadruple therapy<br>* Other names: Bismuth;Drug: Metronidazole<br>* antibiotic of each quadruple therapy<br>* Other names: antibiotic;Drug: Tetracycline<br>* antibiotic of classical quadruple therapy<br>* Other names: antibiotic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eradication rate of Helicobacter pylori | Access eradication rate of H. pylori by intention to treat (ITT) and per-protocol (PP) analysis in each treatment group | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of side effects of each treatment | Score side effects as mild, moderate or severe according to their influence on daily activities | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Helicobacter pylori, Treatment Failure, second-line therapy