Genotypic Resistance-guided Versus Empirical Therapy for H. Pylori Eradication.

Study Overview
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Brief Summary
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This study aims to investigate the efficacy of a 7-day genotypic resistance-guided triple therapy, compared with empirical concomitant therapy, for first-line eradication of H. pylori.

Detailed Description
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Empiric eradication of H. pylori becomes steadily more challenging because of increasing antibiotic resistance. In high-resistance countries where bismuth and/or tetracycline are unavailable (eg; Greece), non-bismuth quadruple therapies are currently recommended as first-line therapeutic options; however, eradication rates >95% are infrequently achieved and even >90% are disputed. Antimicrobial susceptibility-guided therapy is a promising alternative in order to maintain high therapeutic efficacy. However, traditional culture-based susceptibility testing methods have several shortcomings, including they are time-consuming and they do not 100% reflect in vivo eradication. Recent guidelines also recommend the use of molecular testing for evaluation of H. pylori antibiotic susceptibility. Nevertheless, the efficacy of genotypic resistance-guided treatment of H. pylori has been seldom appraised. Therefore, the investigators conducted this prospective randomized controlled trial aiming to investigate the efficacy of a 7-day genotypic resistance-guided triple therapy, compared with empirical concomitant therapy, for first-line eradication of H. pylori.

Official Title
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Genotypic Resistance-guided Triple Therapy Versus Empirical Concomitant Therapy for First-line H. Pylori Eradication.

Conditions
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Helicobacter Pylori Infection

Intervention / Treatment
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* Drug: Esomeprazole 40mg
* Drug: Clarithromycin 500mg
* Drug: Metronidazole 500 mg
* Drug: Amoxicillin 1000 MG
* Drug: Levofloxacin 500mg
* Drug: Rifabutin 150 MG


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive outpatients aged ≥18 years with documented H. pylori infection. Mental and legal ability to provide written informed consent. Exclusion Criteria: previous history of H. pylori eradication therapy history of allergies to the medications used previous esophageal or gastric surgery serious systemic disease pregnancy or lactation.

Ages Eligible for Study
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Minimum Age: 18 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: Genotypic resistance-guided triple therapy<br>In the group of genotypic resistance-guided triple therapy, a molecular assay based on DNA-strip technology was used to determine the genotypic resistance of H. Pylori to clarithromycin (23SrRNA mutations) and fluoroquinolones (gyrA mutations) from gastric biopsy specimens. According to 23SrRNA and gyrA mutational analyses, a 7-day tailored triple therapy therapy was given as follows: Wild-type 23SrRNA: Clarithromycin-based triple therapy comprising esomeprazole 40 mg b.i.d., amoxicillin 1 g b.i.d. and clarithromycin 500 mg b.i.d. 23SrRNA mutated/wild-type gyrA: Levofloxacin-based triple therapy comprising esomeprazole 40 mg b.i.d., amoxicillin 1 g b.i.d. and levofloxacin 500 mg b.i.d. 23SrRNA mutated/gyrA mutated: Rifabutin-based triple therapy comprising esomeprazole 40 mg b.i.d., amoxicillin 1 g t.i.d. and rifabutin 150 mg b.i.d. | Drug: Esomeprazole 40mg<br>* Use in a drug combination for H. pylori eradication<br>Drug: Clarithromycin 500mg<br>* Use in a drug combination for H. pylori eradication<br>Drug: Amoxicillin 1000 MG<br>* Use in a drug combination for H. pylori eradication<br>Drug: Levofloxacin 500mg<br>* Use in a drug combination for H. pylori eradication<br>Drug: Rifabutin 150 MG<br>* Use in a drug combination for H. pylori eradication<br>|
| Active Comparator: Empirical concomitant therapy<br>In the empirical concomitant group, patients received esomeprazole 40mg, amoxicillin 1gr, clarithromycin 500mg and metronidazole 500mg, all b.i.d., for 10-14 days. | Drug: Esomeprazole 40mg<br>* Use in a drug combination for H. pylori eradication<br>Drug: Clarithromycin 500mg<br>* Use in a drug combination for H. pylori eradication<br>Drug: Metronidazole 500 mg<br>* Use in a drug combination for H. pylori eradication<br>Drug: Amoxicillin 1000 MG<br>* Use in a drug combination for H. pylori eradication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of H. pylori eradication | Rate of H. pylori eradication by intention to treat/per protocol in each group at least 6 weeks after treatment completion using the urea breath test. | At least 6 weeks after treatment completion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of adverse effects | Adverse events were investigated by means of a structured clinical interview immediately after the completion of therapy. The subjects were asked to grade the severity of adverse events according to their influence on daily activities, experienced as mild (transient and well tolerated), moderate (causing discomfort and partially interfering with daily activities), or severe (causing considerable interference with daily activities). | At least 6 weeks after treatment completion | 
| Compliance rates | Drug compliance was determined by counting unused medication. For this purpose, any tablet that was not consumed was brought back to the clinic for pill count. Poor compliance was defined as taking less than 80% of the total medication prescribed. | At least 6 weeks after treatment completion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H. pylori, genotypic resistance, tailored therapy, concomitant therapy