Amoxicillin/Metronidazole Based Quadruple Therapy for Helicobacter Pylori Eradication

Study Overview
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Brief Summary
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No trial has examined the the efficacy of amoxicillin and metronidazole based quadruple therapy for Helicobacter pylori treatment. The study aims to compare the effectiveness and safety of 14-day amoxicillin-/metronidazole-based quadruple regiment and classical quadruple regiment for Helicobacter pylori eradication.

Detailed Description
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Helicobacter pylori is the most successful human pathogen infecting an estimated 50% of the global population. It is a common and potentially curable cause of dyspepsia and peptic ulcer disease. Eradication in patients with peptic ulcer or even functional or non-investigated dyspepsia is a cost effective approach. 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. Due to the low efficacy achieved with these treatments, they have been deemed as unethical comparators in clinical trials. As antimicrobial resistance becomes more prevalent worldwide, treatment failure rates are likely to continue increasing, suggesting that new regimens for H pylori eradication must be sought. Bismuth-containing quadruple therapies have been used widely in H. pylori therapy with many permutations of doses and durations and with variable results. Classical bismuth-based quadruple therapy containing a PPI, bismuth, tetracycline and metronidazole has been recommended as the first-line treatment by the Maastricht IV Consensus Conference report and H. pylori Study Group of Chinese Society of Gastroenterology. But this regiment has high rate of side effects because of tetracycline. Standard triple therapy-based, bismuth-containing quadruple Therapy is also an alternative. Though addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin, its use as a first-line treatment is limited in areas of high clarithromycin resistance. Amoxicillin has low resistance rate as well as low percentage of side effects. The combination of amoxicillin and metronidazole in bismuth-containing quadruple therapy may be a better choice, which can avoid clarithromycin resistance and reduce side effects. Therefore, we will do a randomized trial to compare the eradication rate of 14-day amoxicillin and metronidazole based bismuth-containing quadruple therapy with amoxicillin and clarithromycin based quadruple therapy for Helicobacter pylori infection.

Official Title
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Prospective, Randomized Controlled Trial Comparing Amoxicillin and Metronidazole Based Bismuth-containing Quadruple Therapy With Amoxicillin and Clarithromycin Based Quadruple Therapy for First-line Helicobacter Pylori Eradication

Conditions
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Dyspepsia, Peptic Ulcer

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with non-investigated/functional dyspepsia or scarred peptic ulcer with indication of H pylori eradication treatment Ability and willingness to participate in the study and to sign and give informed consent confirmed H pylori infection by at least one of the following methods: C13-urea breath test, histology, rapid urease test or bacterial culture. Exclusion Criteria: patients with peptic ulcer previous H. pylori eradication therapy Age below 18 years major systemic diseases previous gastric surgery pregnancy or breastfeeding allergy to any of the study drugs receipt of anti-secretory therapy, antibiotics or bismuth salts 4 weeks prior to inclusion

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: Amoxicillin/metronidazole<br>Amoxicillin/metronidazole-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, amoxicillin 1000mg bid, 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: Amoxicillin<br>* antibiotic of each quadruple therapy<br>* Other names: antibiotic;Drug: Metronidazole<br>* antibiotic of the amoxicillin/metronidazole-based quadruple therapy<br>* Other names: antibiotic;|
| Active Comparator: Amoxicillin/clarithromycin<br>Amoxicillin/clarithromycin-based quadruple therapy for 14 days: Lansoprazole 30mg bid, Bismuth Potassium Citrate 220mg bid, Amoxicillin 1000mg bid, Clarithromycin 500mg bid | 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: Amoxicillin<br>* antibiotic of each quadruple therapy<br>* Other names: antibiotic;Drug: Clarithromycin<br>* antibiotic of the amoxicillin/clarithromycin-based 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 eradication, antibiotic