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.
Overview
- Phase
- Phase 3
- Intervention
- Pantoprazole 40mg
- Conditions
- Helicobacter Pylori Infection
- Sponsor
- University of Bari
- Enrollment
- 362
- Locations
- 1
- Primary Endpoint
- Eradication rate
- Last Updated
- 5 years ago
Overview
Brief Summary
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
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.
Investigators
Alfredo Di Leo
Professor of University of Bari
University of Bari
Eligibility Criteria
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.
Arms & Interventions
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Pantoprazole 40mg
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Amoxicillin 1000 MG
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Clarithromycin 500mg
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Metronidazole
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Tetracycline 125 MG
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Bismuth Subcitrate
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Rifabutin 150 MG
Tailored therapy
1. 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) 2. 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) 3. 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) 4. Clarithromycin-, tetracycline- and levofloxacin-resistant strain (10 day-therapy): Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Rifabutin 150 mg bid (tablet)
Intervention: Levofloxacin 500mg
Empiric therapy
Either one of the two following 10-day regimens (according to physician's decision): 1. Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) 2. Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid)
Intervention: Pantoprazole 40mg
Empiric therapy
Either one of the two following 10-day regimens (according to physician's decision): 1. Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) 2. Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid)
Intervention: Amoxicillin 1000 MG
Empiric therapy
Either one of the two following 10-day regimens (according to physician's decision): 1. Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) 2. Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid)
Intervention: Clarithromycin 500mg
Empiric therapy
Either one of the two following 10-day regimens (according to physician's decision): 1. Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) 2. Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid)
Intervention: Metronidazole
Empiric therapy
Either one of the two following 10-day regimens (according to physician's decision): 1. Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) 2. Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid)
Intervention: Tetracycline 125 MG
Empiric therapy
Either one of the two following 10-day regimens (according to physician's decision): 1. Pantoprazole 40 mg bid (tablet) Amoxicillin 1000 mg bid (tablet) Clarithromycin 500 mg bid (tablet) Metronidazole 500 mg bid (tablet) 2. Pantoprazole 40 mg bid (tablet) Tetracycline 125 mg + metronidazole 125 mg + bismuth 140 mg in a single tablet (3 tablets qid)
Intervention: Bismuth Subcitrate
Outcomes
Primary Outcomes
Eradication rate
Time Frame: 30 days
Number of participants achieving Helicobacter pylori eradication
Secondary Outcomes
- Treatment withdrawal(10 days)
- Participants' compliance(10 days)
- Adverse events(10 days)