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

NCT ID: NCT04107194

Last Updated: 2021-01-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 362 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-14
• Study Completion Date: 2022-04-14

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.

Conditions

Helicobacter Pylori Infection; Antibiotic Resistant Infection; Antibiotic Resistant Strain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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)

Group Type: EXPERIMENTAL

Pantoprazole 40mg

Intervention Type: DRUG

Proton pump inhibitor

Amoxicillin 1000 MG

Intervention Type: DRUG

Antibiotic

Clarithromycin 500mg

Intervention Type: DRUG

Antibiotic

Metronidazole

Intervention Type: DRUG

Antibiotic

Tetracycline 125 MG

Intervention Type: DRUG

Antibiotic

Bismuth Subcitrate

Intervention Type: DRUG

Antibiotic adjuvant

Rifabutin 150 MG

Intervention Type: DRUG

Antibiotic

Levofloxacin 500mg

Intervention Type: DRUG

Antibiotic

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)

Group Type: ACTIVE_COMPARATOR

Pantoprazole 40mg

Intervention Type: DRUG

Proton pump inhibitor

Amoxicillin 1000 MG

Intervention Type: DRUG

Antibiotic

Clarithromycin 500mg

Intervention Type: DRUG

Antibiotic

Metronidazole

Intervention Type: DRUG

Antibiotic

Tetracycline 125 MG

Intervention Type: DRUG

Antibiotic

Bismuth Subcitrate

Intervention Type: DRUG

Antibiotic adjuvant

Interventions

Pantoprazole 40mg

Proton pump inhibitor

Intervention Type: DRUG

Amoxicillin 1000 MG

Antibiotic

Intervention Type: DRUG

Clarithromycin 500mg

Antibiotic

Intervention Type: DRUG

Metronidazole

Antibiotic

Intervention Type: DRUG

Tetracycline 125 MG

Antibiotic

Intervention Type: DRUG

Bismuth Subcitrate

Antibiotic adjuvant

Intervention Type: DRUG

Rifabutin 150 MG

Antibiotic

Intervention Type: DRUG

Levofloxacin 500mg

Antibiotic

Intervention Type: DRUG

Other Intervention Names

Pantorc; Zimox; Klacid; Flagyl; Ambramicina; Denol; Mycobutin; Levoxacin

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Bari

OTHER

Sponsor Role: lead

Responsible Party

Alfredo Di Leo

Professor of University of Bari

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mariabeatrice Principi, Prof.

Role: PRINCIPAL_INVESTIGATOR

University of Bari

Locations

Michele Barone

Bari, BA, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Michele Barone, Prof.

Role: CONTACT

michele.barone@uniba.it

+39 3477157666

Facility Contacts

Michele Barone

Role: primary

michele.barone@uniba.it

3477157666

References

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.

Reference Type: RESULT

PMID: 27707777 (View on PubMed)

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.

Reference Type: RESULT

PMID: 30038469 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27687850 (View on PubMed)

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.

Reference Type: RESULT

PMID: 27144617 (View on PubMed)

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.

Reference Type: RESULT

PMID: 21188333 (View on PubMed)

Other Identifiers

Policlinic Hospital 6, Bari

Identifier Type: -

Identifier Source: org_study_id