Non-invasive Test-guided Tailored Therapy Versus Empiric Treatment for Helicobacter Pylori Infection. (THD-HP)

University of Bari

Status and phase: Unknown; Phase 3

Conditions: Helicobacter Pylori Infection; Antibiotic Resistant Infection; Antibiotic Resistant Strain

Treatments: Drug: Bismuth Subcitrate; Drug: Amoxicillin 1000 MG; Drug: Rifabutin 150 MG; Drug: Levofloxacin 500mg; Drug: Metronidazole; Drug: Pantoprazole 40mg; Drug: Tetracycline 125 MG; Drug: Clarithromycin 500mg

Study type: Interventional

Funder types: Other

Identifiers

NCT04107194

Policlinic Hospital 6, Bari

Details and patient eligibility

About

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.

Full 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.

Enrollment: 362 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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362 participants in 2 patient groups

Tailored therapy

Experimental group

Description:

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)

Treatment:

Drug: Clarithromycin 500mg

Drug: Tetracycline 125 MG

Drug: Pantoprazole 40mg

Drug: Metronidazole

Drug: Levofloxacin 500mg

Drug: Rifabutin 150 MG

Drug: Amoxicillin 1000 MG

Drug: Bismuth Subcitrate

Empiric therapy

Active Comparator group

Description:

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)

Treatment:

Drug: Clarithromycin 500mg

Drug: Tetracycline 125 MG

Drug: Pantoprazole 40mg

Drug: Metronidazole

Drug: Amoxicillin 1000 MG

Drug: Bismuth Subcitrate