Efficacies of HDDT With or Without Bismuth vs Amoxicillin-metronidazole BQT for First-line H Pylori Eradication

Study Overview
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Brief Summary
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Up to know, three is few large-scale, randomized study prospectively and simultaneously comparing the efficacy, adverse effects and patient compliance of high-dose dual therapy (HDDT) with or without bismuth versus amoxicillin-metronidazole bismuth quadruple therapy (AM-BQT) as first-line regimens for H. pylori eradication. The aims of this study are: to compare the efficacy of HDDT with or without bismuth and AM-BQT as first-line regimens for H. pylori eradication; to compare the patient adherence and adverse effects of these treatment regimens; to investigate factors that may influence H. pylori eradication by these treatment regimens; to identify the effect of H. pylori eradication on the evolution of ecosystem of microbiota, and inflammatory parameters.

Detailed Description
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This prospective multicenter randomized comparative study will be conducted at the National Taiwan University Hospital(NTUH), NTUH Bei-Hu Branch, NTUH Hsin-Chu Branch, Buddhist Tzu Chi General Hospital, and Mennonite Christian Hospital in Hua-Lien City. Patients, aged >= 20, having H. pylori-positive chronic gastritis with/without peptic ulcers (duodenal or gastric ulcers) will be recruited. All undergo endoscopy with biopsy for rapid urease test, histology, and bacterial culture before treatment. If the patients did not receive anti-H. pylori therapy previously, these patients will be invited to enter this study for evaluating the efficacy of these 1st-line regimens. A computed generated random numbers sequence will be blocked into three subgroups, say A, B, and C. After giving written informed consent, each patient will be randomly allocated, to one of three treatment groups: group A - HDDT (rabeprazole 20 mg qid + amoxicillin 750 mg qid for 14 days); group B - Bis-HDDT (rabeprazole 20 mg qid + amoxicillin 750 mg qid + tripotassium dicitrate bismuthate 300 mg qid, for 14 days); group C - AM-BQT (rabeprazole 20 mg bid + tripotassium dicitrate bismuthate 600 mg bid + amoxicillin 1000 mg bid + metronidazole 500 mg tid , for 14 days); All patients will be asked to complete a questionnaire and to record symptoms, drug consumption, and diet content daily during the treatment period. Post-treatment, the patients will be followed up at the Outpatients Clinic to investigate patient adherence and adverse effects of treatment. Four to eight weeks after termination of treatment, H. pylori infection status will be examined by the C13-urea breath test (UBT). The CYP2C19 genotype of each participant will be analyzed by the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. A part of participants, at least 30 cases in each group, will be invited to join a follow-up program for one year for evaluating the changes or evolution of gut microbiota composition, metabolic product, parameters of inflammation and immune response.

Official Title
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Efficacies of High-dose Dual Therapy With or Without Bismuth Versus Amoxicillin-metronidazole Bismuth Quadruple Therapy for First-line Helicobacter Pylori Eradication - A Prospective, Randomized, Comparative Study

Conditions
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Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: High-dose dual therapy (rabeprazole, amoxicillin)
* Drug: Bismuth High-dose dual therapy (rabeprazole, amoxicillin, tripotassium dicitrate bismuthate)
* Drug: Amoxicillin-Metronidazole Bismuth quadruple therapy


Participation Criteria
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Eligibility Criteria
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inclusion criteria: participants having H. pylori related chronic gastritis with/without peptic ulcers who are aged greater than 20 years old and are willing to received first-line eradication therapy. Exclusion criteria: pregnant or nursing woman; serious concomitant illness and malignant tumor of any kind; history of hypersensitivity to test drugs； serious bleeding during the course of this ulcer; previous gastric surgery; receiving bismuth salts, proton pump inhibitors (PPIs), or antibiotics in the previous month.

Ages Eligible for Study
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Minimum Age: 20 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 dual therapy<br>group A - HDDT (rabeprazole 20 mg qid + amoxicillin 750 mg qid, for 14 days) | Drug: High-dose dual therapy (rabeprazole, amoxicillin)<br>* High-dose dual therapy (rabeprazole 20 mg qid + amoxicillin 750 mg qid, for 14 days)<br>* Other names: Antibiotics, Amoxicillin ,Amoxicillin®;|
| Experimental: Bismuth High-dose dual therapy<br>group B - Bis-HDDT (rabeprazole 20 mg qid + amoxicillin 750 mg qid + tripotassium dicitrate bismuthate 300 mg qid, for 14 days) | Drug: Bismuth High-dose dual therapy (rabeprazole, amoxicillin, tripotassium dicitrate bismuthate)<br>* Bismuth-High-dose dual therapy (rabeprazole 20 mg qid + amoxicillin 750 mg qid + tripotassium dicitrate bismuthate 300 mg qid, for 14 days)<br>* Other names: Colloidal Bismuth, Tripotassium dicitrate bismuthate, KCB®;|
| Active Comparator: Amoxicillin-Metronidazole Bismuth quadruple therapy<br>group C - AM-BQT (rabeprazole 20 mg bid + tripotassium dicitrate bismuthate 600 mg bid + amoxicillin 1000 mg bid + metronidazole 500 mg tid, for 14 days) | Drug: Amoxicillin-Metronidazole Bismuth quadruple therapy<br>* Amoxicillin-Metronidazole Bismuth quadruple therapy (rabeprazole 20 mg bid + tripotassium dicitrate bismuthate 600 mg bid + amoxicillin 1000 mg bid + metronidazole 500 mg tid, for 14 days)<br>* Other names: Colloidal Bismuth, Tripotassium dicitrate bismuthate, KCB®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to compare the eradication rate of HDDT with or without bismuth and AM-BQT as first-line regimens for H. pylori eradication. | The eradication rates (efficacy) of these regimens will be evaluated by the results of C13-urea breath test. | 5.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| to compare the patient adherence and frequency of adverse effects of these treatment regimens. | The frequency of adverse events will be evaluated by the number of participant with adverse events and patient adherence will be evaluated by counting unused medication after the treatment. | 5.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Helicobacter pylori, high dose dual therapy, bismuth high-dose dual therapy, bismuth quadruple therapy