CANHelp Working Group Treatment Trials

Study Overview
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Brief Summary
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The CANHelp Working Group Treatment Trials are part of a comprehensive research program carried out by the Canadian North Helicobacter pylori (CANHelp) Working Group. The treatment component involves a series of community-specific trials designed with community input and varying on the specific treatment regimens and number of treatment arms among other study details.

Detailed Description
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The CANHelp Working Group is a collaborative team that links University of Alberta researchers with Canadian northern community leaders and health officials in a collaborative effort to investigate H. pylori infection with the goal of finding solutions to community concerns about health risks. The research program uses a community-driven research approach in northern communities to characterize the burden of disease from H. pylori infection and exchange knowledge with community members and decision makers to identify ways to reduce health risks from this infection. For the participating communities, the treatment trials aim to: Estimate the effectiveness of alternate H. pylori treatment regimens to identify optimal regimens for the local setting Identify factors external to the treatment regimen that influence short- and long-term treatment success

Official Title
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Canadian North Helicobacter Pylori (CANHelp) Working Group Treatment Trials

Conditions
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Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: Standard Triple
* Drug: Sequential
* Drug: Quadruple


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Over 15 years of age Identified as H. pylori infected with a positive urea breath test and/or biopsy-based evidence of H. pylori infection Exclusion Criteria: Allergy to amoxicillin, metronidazole or clarithromycin Antibiotic therapy within 4 weeks prior to randomization Pregnant or breastfeeding Severe cardio-respiratory, pulmonary, endocrine, hepatic or renal disease

Ages Eligible for Study
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Minimum Age: 16 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Triple, treatment naive<br>Standard Triple Therapy for H. pylori: Oral twice-daily doses of rabeprazole (20 mg), amoxicillin (1 g) and clarithromycin (500 mg) One of two treatments randomly assigned to treatment naive participants in Aklavik | Drug: Standard Triple<br>* Oral twice-daily doses of rabeprazole (20 mg), amoxicillin (1 g) and clarithromycin (500 mg)<br>* Other names: Hp-PAC;|
| Active Comparator: Sequential, treatment naive<br>Sequential Therapy for H. pylori: Oral twice-daily doses of rabeprazole (20 mg) and amoxicillin (1 g) on days 1-5, and on days 6-10, rabeprazole (20 mg), metronidazole (500 mg) and clarithromycin (500 mg) One of two treatments randomly assigned to treatment naive participants in Aklavik, Old Crow, Tuktoyaktuk & Fort McPherson | Drug: Sequential<br>* Oral twice-daily doses of rabeprazole (20 mg) and amoxicillin (1 g) on days 1-5, and on days 6-10, rabeprazole (20 mg), metronidazole (500 mg) and clarithromycin (500 mg)<br>* Other names: Sequential Therapy for H. pylori;|
| Active Comparator: Quadruple, treatment naive<br>Quadruple Thearpy for H. pylori: Oral doses of rabeprazole (20 mg) twice daily, metronidazole (500 mg) three times daily, bismuth subsalicylate (Pepto-Bismol) (2 tablets) four times daily and tetracycline (500 mg) four times daily One of two treatments randomly assigned to treatment naive participants in Old Crow, Tuktoyaktuk & Fort McPherson | Drug: Quadruple<br>* Oral doses of rabeprazole (20 mg) twice daily, metronidazole (500 mg) three times daily, bismuth subsalicylate (Pepto-Bismol) (2 tablets) four times daily and tetracycline (500 mg) four times daily<br>* Other names: Quadruple Therapy for H. pylori;|
| Active Comparator: Sequential, previous failure(s)<br>Sequential Therapy for H. pylori: Oral twice-daily doses of rabeprazole (20 mg) and amoxicillin (1 g) on days 1-5, and on days 6-10, rabeprazole (20 mg), metronidazole (500 mg) and clarithromycin (500 mg) One of two treatments randomly assigned to participants who previously failed one or more treatments in Aklavik, Old Crow, Tuktoyaktuk & Fort McPherson | Drug: Sequential<br>* Oral twice-daily doses of rabeprazole (20 mg) and amoxicillin (1 g) on days 1-5, and on days 6-10, rabeprazole (20 mg), metronidazole (500 mg) and clarithromycin (500 mg)<br>* Other names: Sequential Therapy for H. pylori;|
| Active Comparator: Quadruple, previous failure(s)<br>Quadruple Therapy for H. pylori: Oral doses of rabeprazole (20 mg) twice daily, metronidazole (500 mg) three times daily, bismuth subsalicylate (Pepto-Bismol) (2 tablets) four times daily and tetracycline (500 mg) four times daily One of two treatments randomly assigned to participants who previously failed treatment in Aklavik, Old Crow, Tuktoyaktuk & Fort McPherson | Drug: Quadruple<br>* Oral doses of rabeprazole (20 mg) twice daily, metronidazole (500 mg) three times daily, bismuth subsalicylate (Pepto-Bismol) (2 tablets) four times daily and tetracycline (500 mg) four times daily<br>* Other names: Quadruple Therapy for H. pylori;|
| Active Comparator: Sequential, clarithromycin-resistant<br>Sequential Therapy for H. pylori: Oral twice-daily doses of rabeprazole (20 mg) and amoxicillin (1 g) on days 1-5, and on days 6-10, rabeprazole (20 mg), metronidazole (500 mg) and clarithromycin (500 mg) One of two treatments randomly assigned to participants with known clarithromycin resistance in Aklavik | Drug: Sequential<br>* Oral twice-daily doses of rabeprazole (20 mg) and amoxicillin (1 g) on days 1-5, and on days 6-10, rabeprazole (20 mg), metronidazole (500 mg) and clarithromycin (500 mg)<br>* Other names: Sequential Therapy for H. pylori;|
| Active Comparator: Quadruple, clarithromycin-resistant<br>Quadruple Therapy for H. pylori: Oral doses of rabeprazole (20 mg) twice daily, metronidazole (500 mg) three times daily, bismuth subsalicylate (Pepto-Bismol) (2 tablets) four times daily and tetracycline (500 mg) four times daily One of two treatments randomly assigned to participants with known clarithromycin resistance in Aklavik | Drug: Quadruple<br>* Oral doses of rabeprazole (20 mg) twice daily, metronidazole (500 mg) three times daily, bismuth subsalicylate (Pepto-Bismol) (2 tablets) four times daily and tetracycline (500 mg) four times daily<br>* Other names: Quadruple Therapy for H. pylori;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-treatment H. pylori status by urea breath test | Treatment effectiveness, defined as the probability (average risk) of elimination of H. pylori infection following treatment, measured as the proportion of trial participants with a negative post-treatment urea breath test at least 10 weeks following completion of treatment. Using an intention-to-treat analysis, the denominator for this proportion is the number of trial participants assigned treatment. Using a per-protocol analysis, the denominator for this proportion is the number of trial participants who completed treatment and were tested post-treatment. Participants are administered a urea breath test using 13C-labeled urea dissolved in a citric acid solution. We use the following test value classifications for determining the outcome: >=4.0 (Positive for H. pylori infection) Between 2.5 and 4.0 (Borderline; repeat test) Between 2.4 and -1.99 (Negative for H. pylori infection) Less than -2.0 (Uncertain test result, repeat test) | A minimum of 10 weeks after participant has completed treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to treatment regimen | Participants are asked to return blister packs with unused medication so skipped doses can be counted. Participants are also interviewed to obtain details about their adherence to the regimen. | An expected average of 1 week after treatment is completed |