Tailored Vs. Empirical Helicobacter Pylori Infection Treatment

Official title

Susceptibility-guided Vs. Empirical First-line Bismuth Quadruple Therapy of H. Pylori Infection: a National Prospective Multicentric Randomized Controlled Trial.

Overview

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.

Detailed description

A prospective, multicenter, randomized, controlled interventional trial in two arms: intervention group and control group.

Eligible patients will receive oral and written information and will be enrolled after giving written informed consent.

In all patients complete gastroscopy with white light will be performed and endoscopic findings will be recorded. For each patient, gastric body and antral biopsies will be collected. All gastric samples will be tested for H. pylori infection by histopathological examination and PCR. All H. pylori positive samples will be tested for clarithromycin (mutations in the 23S rRNA gene, A2134G, A2142G and A2142C mutations) and levofloxacin resistance (mutations in the gyrA gene) by PCR.

All H. pylori positive patients will be randomized in two groups:

INTERVENTION GROUP: 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).

CONTROL GROUP: 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).

All patients that complete eradication treatment regimen will be evaluated 2 to 4 weeks after performing the eradication control (urea breath test) in a clinical consultation. Eventual adverse effects will be recorded. A negative breath test will define the success of the treatment, while a positive test will define treatment failure. The latter will be managed according to H. pylori infection guidelines.

Interventions

• Diagnostic test Clarithromycin (mutations in the 23S rRNA gene, A2134G, A2142G and A2142C mutations) and levofloxacin resistance (mutations in the gyrA gene) PCR test
  Described in "Arms" section
• Drug Empirically H. pylori eradication treatment with bismuth quadruple therapy (Pylera®)
  Described in "Arms" section
• Drug PPI, amoxicillin 1 g and clarithromycin 500 mg, twice daily, for 10 days
  Administered to patients randomized to Intervention group and with H. pylori clarithromycin-sensitive strain
• Drug PPI, amoxicillin 1g and levofloxacin 250 mg, twice daily, for 10 days
  Administered to patients randomized to Intervention group and with H. pylori clarithromycin-resistant and levofloxacin-sensitive strain
• Drug Bismuth quadruple therapy (Pylera®) for 10 days
  Administered to patients randomized to Intervention group and with H. pylori clarithromycin-resistant and levofloxacin-resistant strain

Primary outcome measures

• Percentage of successful H. pylori eradication treatment in intervention group vs. control group. [Time frame: 12 months]

Secondary outcome measures (3)

• Percentage of H. pylori detection in gastric samples by PCR vs. histopathological examination. [Time frame: 12 months]
• Estimate the prevalence of H. pylori infection in Portugal. [Time frame: 12 months]
• Estimate the prevalence of H. pylori resistance to clarithromycin and levofloxacin in Portugal. [Time frame: 12 months]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• 1st 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
• 2nd phase (endoscopic): upper GI tract neoplasia; hemorrhagic gastritis; upper GI tract varices
• 3rd phase (pathological): H. pylori negative patients

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

Portugal · 1 center

• Unilabs Portugal — Porto

Identifiers

NCT: NCT06200779 · Clinical Study Protocol 1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗