Effectiveness of Rifabutin for Treatment of Helicobacter Pylori

Study Overview
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Brief Summary
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The aim of this study is to determine the effectiveness of rifabutin triple therapy for the treatment of H. pylori infection in the Israeli population. Patients with or without a prior history of H. pylori eradication failure will be randomized to receive one of three possible treatments: Group 1-amoxicillin 1000mg bd and rifabutin 150 mg bd and esomeprazole 40 mg bd Group 2- amoxicillin 1000mg bd and rifabutin 150 mg d and esomeprazole 40 mg bd Group 3- standard of care

Detailed Description
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Patients who present to the outpatient gastroenterology clinic at our institution with a positive diagnostic test for H pylori will be screened. Included patients will undergo randomisation into 3 groups. Randomization will be performed by a random sequence generator to create equal sized groups in boxes of 12. Group 1-amoxicillin 1000mg bd and rifabutin 150 mg bd and esomeprazole 40 mg bd Group 2- amoxicillin 1000mg bd and rifabutin 150 mg d and esomeprazole 40 mg bd Group 3- standard of care Standard of care in previously untreated patients will consist of concomitant treatment (amoxicillin 1000mg, clarithromycin 500 mg, tinidazole 500 mg and esomeprazole all given twice daily for 14 days). In previously treated patients standard of care will consist of bismuth quadruple therapy, quinolone based therapy, or other susceptibility guided treatment where available. Treatment duration will be 14 days in all groups. Patients who are randomised to Group 3 and fail treatment will be offered open label rescue treatment with amoxicillin 1000mg bd, rifabutin 150 mg bd and esomeprazole 40 mg bd (14 days).

Official Title
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Effectiveness of Rifabutin Triple Therapy for First-line and Rescue Treatment of Helicobacter Pylori Infection

Conditions
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Helicobacter Infections, Resistance Bacterial, Gastritis H Pylori

Intervention / Treatment
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* Drug: Rifabutin
* Drug: Amoxicillin
* Drug: Esomeprazole
* Drug: Clarithromycin
* Drug: Tinidazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients presenting to outpatient clinic with evidence of H. pylori infection Exclusion Criteria: allergy to any of the study drugs prior exposure to rifamycin drugs inability to provide informed consent pregnancy or lactation liver disease haematological disease renal failure active malignancy immune suppression patients not expected to benefit from Helicobacter pylori eradication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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
Interventional Model Description: Randomized, open-label, non-blinded
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Rifabutin full dose<br>oral amoxicillin 1000mg bd and rifabutin 150 mg bd and esomeprazole 40 mg bd 14 days | Drug: Rifabutin<br>* 150 mg<br>* Other names: mycobutin®;Drug: Amoxicillin<br>* 1000 mg<br>* Other names: Amoxil®;Drug: Esomeprazole<br>* 40 mg<br>* Other names: nexium;|
| Active Comparator: Rifabutin low dose<br>oral amoxicillin 1000mg bd and rifabutin 150 mg d and esomeprazole 40 mg bd 14 days | Drug: Rifabutin<br>* 150 mg<br>* Other names: mycobutin®;Drug: Amoxicillin<br>* 1000 mg<br>* Other names: Amoxil®;Drug: Esomeprazole<br>* 40 mg<br>* Other names: nexium;|
| Active Comparator: Standard of Care<br>Standard of care in previously untreated patients will consist of concomitant treatment (oral amoxicillin 1000mg, clarithromycin 500 mg, tinidazole 500 mg and esomeprazole 40 mg all given twice daily for 14 days). In previously treated patients standard of care will consist of bismuth quadruple therapy, quinolone based therapy, or other susceptibility guided treatment where available | Drug: Amoxicillin<br>* 1000 mg<br>* Other names: Amoxil®;Drug: Esomeprazole<br>* 40 mg<br>* Other names: nexium;Drug: Clarithromycin<br>* 500 mg<br>* Other names: Biaxin®;Drug: Tinidazole<br>* 500 mg<br>* Other names: protocide®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success of H. pylori treatment | Negative 13C-urea breath test or Helicobacter pylori Stool Ag | 6 weeks following end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events | Daily entry of Likert scale (0-10) for the following parameters: diarrhea, nausea, abdominal pain, dyspepsia, reflux, loss of appetite, asthenia and others (free text). Adverse effects leading to treatment discontinuation. Serious adverse events leading to leading to patient's hospitalization, disability, or death, or to birth defects on pregnant patients | 14 days treatment | 
| Compliance with H. pylori treatment | Assessed by diary entry twice daily. If more than 80% of pills taken, patient considered to be treatment compliant. | 14 days treatment |