A Trial of Standard vs Half Dose Rabeprazole, Clarithromycin, Metronidazole and Amoxicillin in the Treatment of Helicobacter Pylori Infection

Study Overview
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Brief Summary
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The proposed study will test the hypothesis that H. pylori can be eradicated successfully (>85%) using half-or full-dose concomitant non-bismuth quadruple therapy regimen: rabeprazole, amoxicillin, clarithromycin and metronidazole twice daily for 7 days in patients with peptic ulcers and H. pylori related gastritis. Two hundred patients from the outpatient department and the endoscopy unit at AUBMC will be enrolled in this open-label trial. Patients with positive CLO tests or urea breath tests, documenting H.pylori infection, will be randomized into one of two groups: Full dose or half dose the concomitant regimen, with 100 patients in each group. Compliance and side effects will be assessed, and a urea breath test will be done for all patients after 4 weeks of therapy completion to evaluate eradication rates. Success of therapy will be evaluated according to intent-to treat and per-protocol analyses.

Detailed Description
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Infection with H. pylori has been linked with chronic active gastritis, peptic ulcer disease, adenocarcinoma and Non-Hodgkin's lymphoma of the stomach. Eradication of this organism has been recommended for patients with peptic ulcer disease, low-grade gastric mucosa-associated lymphoid tissue lymphoma, atrophic gastritis, unexplained iron deficiency anemia, chronic idiopathic thrombocytopenic purpura, as well as first-degree relatives of gastric cancer patients. Guidelines still recommend using triple therapy regimen of PPI, clarithromycin and amoxicillin/metronidazole twice daily for 7 to 14 days. Over the years, it has become clear that the first-line triple therapy is loosing efficacy worldwide with PP and ITT eradication rates inferior to 80%. Antimicrobial resistance plays an important role in some of these failures. Major H. pylori study groups in the world have agreed that alternative treatment regimens are urgently needed. So far, 2 alternative treatment regimens have shown superiority over the first-line treatment protocols: the sequential therapy consisting of a combination of amoxicillin and a PPI twice a day for 5 days followed by another 5 days of the PPI plus clarithromycin and tinidazole/metronidazole, and the concomitant non-bismuth quadruple regimen consisting of PPI, clarithromycin, metronidazole, and amoxicillin twice daily. The proposed study will test the hypothesis that H. pylori can be eradicated successfully (>85%) using half-or full-dose concomitant non-bismuth quadruple therapy regimen: rabeprazole, amoxicillin, clarithromycin and metronidazole twice daily for 7 days in patients with peptic ulcers and H. pylori related gastritis. Two hundred patients from the outpatient department and the endoscopy unit at AUBMC will be enrolled in this open-label trial. Patients with positive CLO tests or urea breath tests, documenting H.pylori infection, will be randomized into one of two groups: Full dose or half dose the concomitant regimen, with 100 patients in each group. Compliance and side effects will be assessed, and a urea breath test will be done for all patients after 4 weeks of therapy completion to evaluate eradication rates. Success of therapy will be evaluated according to intent-to treat and per-protocol analyses.

Official Title
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A Randomized Trial of Standard vs Half Dose Rabeprazole, Clarithromycin, Metronidazole and Amoxicillin in the Treatment of Helicobacter Pylori Infection

Conditions
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Helicobacter Infections

Intervention / Treatment
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* Drug: Rabeprazole, metronidazole, Clarithromycin, Amoxicillin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: documented H.pylori infection by a CLO test or a Urea Breath Test sign the informed consent Exclusion Criteria: Age under 18 or older than 80 years Allergies to any of the drugs used Recent antibiotic therapy (within 2 weeks of enrolment) Severe ulcers or bleeding Gastric perforation or obstruction Previous gastrectomy Gastric cancer Pregnancy or lactation Prior eradication therapy for H. pylori Severe concomitant disease or condition making the treatment unlikely to be effective i.e. alcoholism, drug addiction, and history of poor compliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 |
| --- | --- |
| Active Comparator: Full Dose<br>Full dose of Rabeprazole (20mg), metronidazole (500mg), Clarithromycin (500mg) and Amoxicillin (1000mg) twice daily for a period of 7 days. | Drug: Rabeprazole, metronidazole, Clarithromycin, Amoxicillin<br>* Full dose arm:Rabeprazole (20mg), metronidazole (500mg), Clarithromycin (500mg) and Amoxicillin (1000mg) twice daily for a period of 7 days. Half dose arm: Rabeprazole (10mg), metronidazole (250mg), Clarithromycin (250mg) and Amoxicillin (500mg) twice daily for a period of 7 days.<br>* Other names: Amoxicillin: Amoxil;|
| Experimental: Half dose<br>Rabeprazole (10mg), metronidazole (250mg), Clarithromycin (250mg) and Amoxicillin (500mg) twice daily for a period of 7 days. | Drug: Rabeprazole, metronidazole, Clarithromycin, Amoxicillin<br>* Full dose arm:Rabeprazole (20mg), metronidazole (500mg), Clarithromycin (500mg) and Amoxicillin (1000mg) twice daily for a period of 7 days. Half dose arm: Rabeprazole (10mg), metronidazole (250mg), Clarithromycin (250mg) and Amoxicillin (500mg) twice daily for a period of 7 days.<br>* Other names: Amoxicillin: Amoxil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with negative urea breath test post treatment | 30 days post treatment completion, patients will do a Urea Breath Test (a test that is regularly used to check for H. Pylori infection in the stomach) to check whether H. Pylori has been eradicated from the stomach or not. | 30 days post treatment completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events as a Measure of Safety and Tolerability | we will check for nausea, vomiting, metallic taste, diarrhea, and abdominal pain during the 7 days of the treatment period in each patient. | during the 7 days of the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Helicobacter pylori infection, quadruple therapy, Amoxicillin, Metronidazole, Clarithromycin, Rabeprazole