Tailored Vs. Empirical Helicobacter Pylori Infection Treatment

NCT06200779 | Not Yet Recruiting Phase 4

• 1 other identifier: Clinical Study Protocol 1
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Helicobacter pylori (Hp) is a gram-negative bacterium that colonizes human gastric mucosa and is associated with chronic gastritis that can progress to severe complications such as peptic ulcer disease, gastric adenocarcinoma and gastric mucosa-associated lymphoid tissue lymphoma. More than half of the world's population is infected with H. pylori and Portugal is one of the countries with the highest Hp burden. All of infected patients should be treated, however, H. pylori treatment is challenged by the continuously rising antibiotic resistance which has reached alarming levels worldwide. For this reason, it is now well accepted that tailoring treatment of H. pylori infection based on systematic antimicrobial susceptibility testing is useful to avoid the increase of antibiotic resistance. Our aims are to determine prospectively the efficacy and safety of first-line H. pylori eradication treatment based on resistance profile (determined by molecular methods) vs. empirical bismuth quadruple therapy, to evaluate the accuracy of H. pylori detection by polymerase chain reaction (PCR) (vs. histopathological examination) and to estimate the prevalence of H. pylori infection and H. pylori resistance to clarithromycin and levofloxacin in Portugal. This prospective study will be the first national study to investigate the benefits of tailored H. pylori eradication treatment. The investigators expect that this project will be able to demonstrate the non-inferiority of susceptibility-guided treatment comparing with empirical therapy, and our results may change H. pylori treatment recommendations by systematically applying antibiotic susceptibility testing before prescribing eradication therapy.

Conditions

Helicobacter Pylori Infection

Keywords

Helicobacter pylori; Antibiotic resistance; Eradication treatment; Molecular pathology

Outcome Measures

Primary Outcomes (1)

• Percentage of successful H. pylori eradication treatment in intervention group vs. control group.

  This comparation will allow the investigators to show the non-inferiority of susceptibility-guided treatment comparing with empirical therapy

  12 months

Secondary Outcomes (3)

• Percentage of H. pylori detection in gastric samples by PCR vs. histopathological examination.

  12 months

• Estimate the prevalence of H. pylori infection in Portugal.

  12 months

• Estimate the prevalence of H. pylori resistance to clarithromycin and levofloxacin in Portugal.

  12 months

Study Arms (2)

Intervention group

ACTIVE COMPARATOR

Patients randomized to the Intervention group will receive a prescription for oriented H. pylori eradication treatment according to the following rules: a) clarithromycin-sensitive strain (independently of levofloxacin resistance test result) - PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days; b) clarithromycin-resistant and levofloxacin-sensitive strain - PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days; c) clarithromycin-resistant and levofloxacin-resistant strain - bismuth quadruple therapy (Pylera®) for 10 days. At least 4 weeks after stopping antibiotics (and at least 2 weeks after stopping PPIs), an eradication control test will be carried out using a respiratory test (urea breath test) or endoscopic biopsies (if clinical indication for that).

Diagnostic Test: Clarithromycin (mutations in the 23S rRNA gene, A2134G, A2142G and A2142C mutations) and levofloxacin resistance (mutations in the gyrA gene) PCR test; Drug: PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days; Drug: PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days; Drug: Bismuth quadruple therapy (Pylera®) for 10 days

Control group

ACTIVE COMPARATOR

Patients randomized to the Control group will receive a prescription for empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®) for 10 days. At least 4 weeks after stopping antibiotics (and at least 2 weeks after stopping PPIs), an eradication control test will be carried out using a respiratory test (urea breath test) or endoscopic biopsies (if clinical indication for that).

Drug: Empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®)

Interventions

Clarithromycin (mutations in the 23S rRNA gene, A2134G, A2142G and A2142C mutations) and levofloxacin resistance (mutations in the gyrA gene) PCR test DIAGNOSTIC_TEST

Described in "Arms" section

Intervention group

Empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®) DRUG

Described in "Arms" section

Control group

PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days DRUG

Administered to patients randomized to Intervention group and with H. pylori clarithromycin-sensitive strain

Intervention group

PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days DRUG

Administered to patients randomized to Intervention group and with H. pylori clarithromycin-resistant and levofloxacin-sensitive strain

Intervention group

Bismuth quadruple therapy (Pylera®) for 10 days DRUG

Administered to patients randomized to Intervention group and with H. pylori clarithromycin-resistant and levofloxacin-resistant strain

Intervention group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals older than 18 years old scheduled for upper GI endoscopy with indication for gastric biopsies (clinical or endoscopic findings)

You may not qualify if:

• st phase (clinical): patients who had received antimicrobial therapy 1 month prior to endoscopy; patients who had received proton pump inhibitor (PPI) therapy 2 weeks prior to endoscopy; patients who had ever received H. pylori eradication therapy (despite its efficacy); history of previous gastrectomy; non-Portuguese nationality; pregnant or breastfeeding women; women of childbearing age without effective contraception; suspected or documented allergy to amoxicillin; serious comorbidities (ASA 3 or more); ongoing medication with anticoagulants
• nd phase (endoscopic): upper GI tract neoplasia; hemorrhagic gastritis; upper GI tract varices
• rd phase (pathological): H. pylori negative patients

Sponsors & Collaborators

• Manuel Coelho da Rocha: lead

Study Sites (1)

Unilabs Portugal

Porto, Porto District, 4150-178, Portugal

Location

MeSH Terms

Interventions

Mutation; Amoxicillin; Clarithromycin; WW Domain-Containing Oxidoreductase; Levofloxacin

Intervention Hierarchy (Ancestors)

Genetic Variation; Genetic Phenomena; Ampicillin; Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Short Chain Dehydrogenase-Reductases; NAD (+) and NADP (+) Dependent Alcohol Oxidoreductases; Alcohol Oxidoreductases; Oxidoreductases; Enzymes; Enzymes and Coenzymes; Tumor Suppressor Proteins; Neoplasm Proteins; Proteins; Amino Acids, Peptides, and Proteins; Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Intervention group: Patients will receive a prescription for oriented H. pylori eradication treatment according to the following rules: a) clarithromycin-sensitive strain (independently of levofloxacin resistance test result) - PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days; b) clarithromycin-resistant and levofloxacin-sensitive strain - PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days; c) clarithromycin-resistant and levofloxacin-resistant strain - bismuth quadruple therapy (Pylera®) for 10 days. Control Group: Patients will receive a prescription for empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®) for 10 days.

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: January 11, 2024
• Study Start: September 1, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: December 20, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting in May 2025

Locations

PT (1)