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

Overview

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 Title of Study: “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.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: February 14, 2021

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.

Interventions

  • Drug: Pantoprazole 40mg
    • Proton pump inhibitor
  • Drug: Amoxicillin 1000 MG
    • Antibiotic
  • Drug: Clarithromycin 500mg
    • Antibiotic
  • Drug: Metronidazole
    • Antibiotic
  • Drug: Tetracycline 125 MG
    • Antibiotic
  • Drug: Bismuth Subcitrate
    • Antibiotic adjuvant
  • Drug: Rifabutin 150 MG
    • Antibiotic
  • Drug: Levofloxacin 500mg
    • Antibiotic

Arms, Groups and Cohorts

  • Experimental: Tailored therapy
    • 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)
  • Active Comparator: Empiric therapy
    • 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)

Clinical Trial Outcome Measures

Primary Measures

  • Eradication rate
    • Time Frame: 30 days
    • Number of participants achieving Helicobacter pylori eradication

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Bari
  • Provider of Information About this Clinical Study
    • Principal Investigator: Alfredo Di Leo, Professor of University of Bari – University of Bari
  • Overall Official(s)
    • Mariabeatrice Principi, Prof., Principal Investigator, University of Bari
  • Overall Contact(s)
    • Michele Barone, Prof., +39 3477157666, michele.barone@uniba.it

Citations Reporting on Results

Malfertheiner P, Megraud F, O'Morain CA, Gisbert JP, Kuipers EJ, Axon AT, Bazzoli F, Gasbarrini A, Atherton J, Graham DY, Hunt R, Moayyedi P, Rokkas T, Rugge M, Selgrad M, Suerbaum S, Sugano K, El-Omar EM; European Helicobacter and Microbiota Study Group and Consensus panel. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut. 2017 Jan;66(1):6-30. doi: 10.1136/gutjnl-2016-312288. Epub 2016 Oct 5.

Iannone A, Giorgio F, Russo F, Riezzo G, Girardi B, Pricci M, Palmer SC, Barone M, Principi M, Strippoli GF, Di Leo A, Ierardi E. New fecal test for non-invasive Helicobacter pylori detection: A diagnostic accuracy study. World J Gastroenterol. 2018 Jul 21;24(27):3021-3029. doi: 10.3748/wjg.v24.i27.3021.

Giorgio F, Ierardi E, Sorrentino C, Principi M, Barone M, Losurdo G, Iannone A, Giangaspero A, Monno R, Di Leo A. Helicobacter pylori DNA isolation in the stool: an essential pre-requisite for bacterial noninvasive molecular analysis. Scand J Gastroenterol. 2016 Dec;51(12):1429-1432. doi: 10.1080/00365521.2016.1216592. Epub 2016 Aug 9.

Drossman DA. Functional Gastrointestinal Disorders: History, Pathophysiology, Clinical Features and Rome IV. Gastroenterology. 2016 Feb 19:S0016-5085(16)00223-7. doi: 10.1053/j.gastro.2016.02.032. Online ahead of print.

De Francesco V, Giorgio F, Hassan C, Manes G, Vannella L, Panella C, Ierardi E, Zullo A. Worldwide H. pylori antibiotic resistance: a systematic review. J Gastrointestin Liver Dis. 2010 Dec;19(4):409-14.

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.