10-day Versus 14-day Concomitant PAMC as First-line Treatment Strategy for the Eradication of H. Pylori Infection
Condition: Helicobacter Pylori Infection
MeSH terms: Infections; Communicable Diseases
Study type: Interventional
Phase: Phase 4

Summary: 
      Helicobacter pylori (H. pylori) infection is highly associated with gastrointestinal
      disorders, including peptic ulcer disease, gastric cancer, and gastric mucosa associated
      lymphoid tissue lymphoma.1 In 1994, H. pylori was classified as a group carcinogen by the
      International Agency for Research on Cancer. Since then, many consensus conferences and
      clinical guidelines worldwide have been established for the treatment of H. pylori infection.

      Despite H. pylori infecting an estimated 50% of the global population,there is no universally
      effective regimen in everyday clinical practice. The current European Helicobacter Study
      Group Guidelines for the first line empirical treatment of the H. pylori infection propose a
      variety of treatment strategies, as optimal treatment of H. pylori infection requires careful
      attention to local antibiotic resistance and eradication patterns. Most recently, the Toronto
      Consensus for the Treatment of Helicobacter pylori Infection in Adults strongly recommended
      that all H. pylori eradication regimens now be given for 14 days. Recommended first-line
      strategies include concomitant nonbismuth quadruple therapy (proton pump inhibitor [PPI] +
      amoxicillin + metronidazole + clarithromycin [PAMC]) and traditional bismuth quadruple
      therapy (PPI + bismuth + metronidazole + tetracycline [PBMT]).The aforementioned statement by
      an international working group of specialists chosen by the Canadian Association of
      Gastroenterology is of the outmost importance, especially in countries with increased
      antibiotic resistance, like Greece, with resistance rates >20% to clarithromycin and >40% to
      metronidazole.
    

Detailed description: 
      In Greece, while the efficacy of the 10-day concomitant PAMC scheme has been recently
      established,to our knowledge no head-to-head comparison evaluating treatment time (10 versus
      14 days) of the same therapeutic regimen has been tried out. We decided to conduct a
      randomized double blind controlled clinical study comparing the 10-day versus the 14-day
      concomitant PAMC therapeutic scheme as first-line treatment strategy for the eradication of
      H. pylori infection, in a country of increased dual resistance to clarithromycin and
      metronidazole (where bismuth is unavailable). The primary end point of our study will be
      treatment efficacy (primary and secondary antibiotic resistance), while secondary end points
      will be patient compliance and safety.

      This open labeled prospective randomized trial will be held at the Army Share Fund Hospital
      (NIMTS), in Athens, Greece, and will be conducted by the Hospital's Department of
      Gastroenterology. Written informed consent will obtained from all participants before
      enrollment. The study must be approved before hand by the Institutional Review Board of
      Hospital.

      Interventions A physician will be recruited so as to obtain the patients' demographic data
      and medical history. Using sealed envelopes, eligible patients will be randomized in two
      groups, with a research assistant assigning the therapies according to the treatment
      allocations kept in the envelopes. In the first group, patients will be assigned to a 10-day
      concomitant PAMC therapy (40mg esomeprazole twice daily, 500mg clarithromycin twice daily,
      1gr amoxicillin twice daily, and 500mg metronidazole twice daily). In the second group,
      patients will be assigned to the same concomitant PAMC therapy for 14days. Each envelope will
      contain precise written instructions regarding the treatment schedule, dosing, and time of
      medication ingestion, while further instructions will be available, if needed, via the
      telephone.

      Follow-up and outcome To confirm compliance, all patients will be asked to bring their
      remaining medication 5 days after the end of the treatment where we will count the rest of
      their pills. Patients with a compliance <80% will be excluded from the study per protocol
      (PP) analysis. Patients will also be interviewed for reasons responsible for missing any
      doses of the regimens, as well as for the occurrence of any new or worsened medical
      conditions that led them to seek medical attention. Adverse events will be classified as
      minor or major, with the later leading to discontinuation of the treatment.

      Four weeks after the treatment period (with no administration of PPIs or any antibiotics), we
      will confirm H. pylori eradication using C13-UBT by a staff member who will be blind to the
      eradication arm of each patient. In case of treatment failure, a repeated endoscopy will be
      performed with biopsy specimens being taken (two from the antrum and two from the body of the
      stomach). Biopsy specimens will be cultured and antibiotic susceptibility will be determined
      for amoxicillin, tetracycline, clarithromycin, metronidazole, and levofloxacin with the aid
      of the agar dilution test, according to the standard European protocol.14,15 The
      microbiologist who will be performing the agar dilution test will be blinded to the
      treatment. If first-line eradication therapy fails, second-line therapy will be administered,
      according to antibiotic susceptibility.

      Statistical analysis In this study, a clinically significant difference for eradication
      between the two groups will be 15%. In order to achieve 80% power for detecting this
      difference, along with an alpha level of 0.05 and an allocation ratio of 1:1, we calculated a
      needed sample of 364 patients. Since this is a convenient clinical sample, the study will be
      terminated either by reaching this number of patients or by the study's timeline limitation.
      Baseline characteristics will be compared and the difference of the observed eradication
      rates between the study groups will be assessed. The results of this study will be analyzed
      in an intention to treat (ITT) and a PP population. The ITT analysis will include all
      randomized patients who will have taken at least one dose of the study medication (regardless
      of compliance). The patients whose infection statuses will be unknown following treatment
      will be considered treatment failures for the purposes of the ITT analysis. The PP analysis
      will include patients with at least 80% compliance (excluding the patients with unknown H.
      pylori status following therapy and those with major protocol violations).
    

Intervention name(s): Esomeprazole
Intervention type(s): Drug
Intervention description(s): dosage difference
Intervention MeSH terms: Esomeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment