Non-invasive Test-guided Tailored Therapy Versus Empiric Treatment for Helicobacter Pylori Infection.

Study Overview
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Brief Summary
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The aim of our study will be to assess in an open-label, multicenter, randomized controlled trial whether a tailored therapy guided by a non-invasive antibiotic susceptibility test on stool samples achieves higher Helicobacter eradication rates than an empiric antibiotic regimen. For this purpose, consecutive patients with dyspeptic symptoms, diagnosis of Helicobacter pylori infection and naïve to eradicating treatments will be allocated to either of the two intervention arms.

Detailed Description
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Study design: Eligible subjects will be defined by the positivity to at least 2 out of 4 tests for Helicobacter pylori infection diagnosis (i.e. histology, rapid urease test, urea breath test and serology). Stool samples and gastric biopsy specimens of eligible patients will be analyzed at enrollment, using real time-polymerase chain reaction (RT-PCR) to detect bacterial DNA mutations conferring resistance to amoxicillin, clarithromycin, tetracycline, metronidazole, and levofloxacin. Participants allocated to the tailored intervention arm will receive an antibiotic combination therapy according to the result of stool sample molecular analysis. Participants allocated to the empiric intervention arm will be treated by either a quadruple concomitant or bismuth-containing regimen, according to the 2017 European Helicobacter pylori management guidelines. In all participants, infection eradication will be evaluated 30 days after treatment end, using urea breath test. We will also assess the diagnostic accuracy of the RT-PCR on fecal samples in detecting bacterial antibiotic resistances, using the RT-PCR on gastric biopsy specimens as the reference standard.

Official Title
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Comparison Between Tailored Therapy Guided by a Non-invasive Antibiotic Susceptibility Test and Empiric Treatment for First-line Helicobacter Pylori Eradication in Patients With Dyspepsia: a Randomized Controlled Trial.

Conditions
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Helicobacter Pylori Infection, Antibiotic Resistant Infection, Antibiotic Resistant Strain

Intervention / Treatment
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* Drug: Pantoprazole 40mg
* Drug: Amoxicillin 1000 MG
* Drug: Clarithromycin 500mg
* Drug: Metronidazole
* Drug: Tetracycline 125 MG
* Drug: Bismuth Subcitrate
* Drug: Rifabutin 150 MG
* Drug: Levofloxacin 500mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: presence of dyspeptic symptoms, according to Rome IV criteria; Helicobacter pylori infection diagnosis by the positivity of at least 2 out of 4 diagnostic tests (i.e. histology, rapid urease test, urea breath test, and serology); naive to Helicobacter pylori treatment; written informed consent. Exclusion Criteria: previous Helicobacter pylori treatment; diagnosis of gastric cancer or other diseases requiring surgery; contraindications to upper endoscopy; chronic diarrhea; known allergy to any drugs used in the intervention and control arm.

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
Interventional Model Description: Open-label, multicenter, parallel-arm randomized controlled trial
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tailored therapy<br>Clarithromycin-sensitive strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) Clarithromycin-resistant and tetracycline-sensitive strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid) Clarithromycin- and tetracycline-resistant and levofloxacin-sensitive strain (10 day- therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Levofloxacin 500 mg bid (tablet) Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet) | Drug: Pantoprazole 40mg<br>* Proton pump inhibitor<br>* Other names: Pantorc;Drug: Amoxicillin 1000 MG<br>* Antibiotic<br>* Other names: Zimox;Drug: Clarithromycin 500mg<br>* Antibiotic<br>* Other names: Klacid;Drug: Metronidazole<br>* Antibiotic<br>* Other names: Flagyl;Drug: Tetracycline 125 MG<br>* Antibiotic<br>* Other names: Ambramicina;Drug: Bismuth Subcitrate<br>* Antibiotic adjuvant<br>* Other names: Denol;Drug: Rifabutin 150 MG<br>* Antibiotic<br>* Other names: Mycobutin;Drug: Levofloxacin 500mg<br>* Antibiotic<br>* Other names: Levoxacin;|
| Active Comparator: Empiric therapy<br>Either one of the two following 10-day regimens (according to physician's decision): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid) | Drug: Pantoprazole 40mg<br>* Proton pump inhibitor<br>* Other names: Pantorc;Drug: Amoxicillin 1000 MG<br>* Antibiotic<br>* Other names: Zimox;Drug: Clarithromycin 500mg<br>* Antibiotic<br>* Other names: Klacid;Drug: Metronidazole<br>* Antibiotic<br>* Other names: Flagyl;Drug: Tetracycline 125 MG<br>* Antibiotic<br>* Other names: Ambramicina;Drug: Bismuth Subcitrate<br>* Antibiotic adjuvant<br>* Other names: Denol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Eradication rate | Number of participants achieving Helicobacter pylori eradication | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Any adverse event occurring during the 10-day treatment | 10 days | 
| Participants' compliance | Number of assumed tablets divided by the total number of prescribed tablets | 10 days | 
| Treatment withdrawal | Withdrawal of any drug included in the prescribed regimen | 10 days |