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

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Helicobacter Pylori Infection; Antibiotic Resistant Infection; Antibiotic Resistant Strain
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Anticipated): 362
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Michele Barone, Prof.; Phone Number: +39 3477157666; Email: michele.barone@uniba.it

Study Locations

• Italy
  • BA
    • Bari, BA, Italy, 70124
      • Recruiting
      • Michele Barone
      • Contact: Michele Barone; Phone Number: 3477157666; Email: michele.barone@uniba.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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)	Drug: Pantoprazole 40mg; Proton pump inhibitor; Other Names: Pantorc; Drug: Amoxicillin 1000 MG; Antibiotic; Other Names: Zimox; Drug: Clarithromycin 500mg; Antibiotic; Other Names: Klacid; Drug: Metronidazole; Antibiotic; Other Names: Flagyl; Drug: Tetracycline 125 MG; Antibiotic; Other Names: Ambramicina; Drug: Bismuth Subcitrate; Antibiotic adjuvant; Other Names: Denol; Drug: Rifabutin 150 MG; Antibiotic; Other Names: Mycobutin; Drug: Levofloxacin 500mg; Antibiotic; Other Names: Levoxacin
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)	Drug: Pantoprazole 40mg; Proton pump inhibitor; Other Names: Pantorc; Drug: Amoxicillin 1000 MG; Antibiotic; Other Names: Zimox; Drug: Clarithromycin 500mg; Antibiotic; Other Names: Klacid; Drug: Metronidazole; Antibiotic; Other Names: Flagyl; Drug: Tetracycline 125 MG; Antibiotic; Other Names: Ambramicina; Drug: Bismuth Subcitrate; Antibiotic adjuvant; Other Names: Denol

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy parameters	Sensitivity, specificity, positive predictive value, negative predictive value, positive and negative likelihood ratio, and accuracy of the RT-PCR on fecal samples for the detection of antibiotic resistances	30 days

Collaborators and Investigators

• Sponsor: University of Bari
• Investigators: Principal Investigator: Mariabeatrice Principi, Prof., University of Bari

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2020
• Primary Completion (Anticipated): February 14, 2021
• Study Completion (Anticipated): April 14, 2022

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 25, 2019
• First Posted (Actual): September 27, 2019

Study Record Updates

• Last Update Posted (Actual): January 12, 2021
• Last Update Submitted That Met QC Criteria: January 11, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Communicable Diseases; Helicobacter Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP1A2 Inhibitors; Antacids; Anti-Infective Agents, Urinary; Renal Agents; Metronidazole; Rifabutin; Amoxicillin; Clarithromycin; Levofloxacin; Bismuth; Pantoprazole; Tetracycline; Bismuth tripotassium dicitrate
• Other Study ID Numbers: Policlinic Hospital 6, Bari

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No