Relation of Metabolic Rate of Omeprazole and Eradication of Helicobacter Pylori Infection
Condition: Duodenal Ulcer; Helicobacter Pylori Infection
MeSH terms: Infections; Communicable Diseases; Helicobacter Infections; Duodenal Ulcer
Study type: Interventional
Phase: Phase 4

Summary: 
      The aims of this study are (1) to evaluate the prevalence rate of PM of CYP2C19 in our
      country; (2) to evaluate the efficacy of dual therapy with different dose of omeprazole and
      amoxicillin; (3) to judge the relationship of genotype of CYP2C19 and the eradication rate of
      dual therapy in the peptic ulcer patients; (4) to try to find out a predictor of success of
      dual therapy and an optimal dose of dual therapy as first-line and rescue anti-Helicobacter
      pylori regimen.
    

Detailed description: 
      Anti-H. pylori therapy is now recommended in patients with peptic ulcer disease associated
      with bacterial infection. Dual therapy containing one PPI and amoxicillin has been suggested
      to be a better treatment than classical triple therapy containing bismuth, metronidazole, and
      tetracycline for H. pylori eradication due to its better compliance and fewer side effects.
      However, the variation in the eradication rate among different studies has limited its
      clinical application. Nonetheless, the amoxicillin-based dual therapy, with very rare
      prevalence of primary and secondary antibiotic resistance, has the potential to be an optimal
      first-line and rescue anti-Helicobacter pylori regimen if the confounding factors that cause
      the labile treatment outcome can be clarified. Cytochrome P450 2C19(CYP2C19), the enzyme that
      metabolizes omeprazole, was found to have genetic polymorphism in its enzyme activity. The
      percentage of poor metabolizer(PM) of CYP2C19 was much higher in Oriental(18~23%) comparing
      to Caucasian(3~5%).

      The aims of this study is to try to find out a predictor of success of dual therapy and an
      optimal dose of dual therapy as first-line and rescue anti-Helicobacter pylori regimen. About
      130 patients with Hp positive duodenal ulcer will be enrolled and allocated randomly into one
      of four treatment groups:Group A：omeprazole 20mg bid 2wk + amoxicillin 500mg qid 2wk; Group
      B：omeprazole 20mg bid 2wk + amoxicillin 250mg qid 2wk; Group C：omeprazole 20mg qd 2wk +
      amoxicillin 500mg qid 2wk; Group D：omeprazole 20mg qd 2wk + amoxicillin 250mg qid 2wk. All
      patients will receive endoscopic exam with biopsy again within 1~2 months after the end of
      treatment. The status of H. pylori infection was examined by endoscopy or the 13C-urea breath
      test (if the patients refused the second endoscopy). Biopsy from the antrum and body will be
      taken for the culture, histology and CLO test. Twenty-four hours intragastric pH measurements
      will be performed on 6 randomly selective patients of each group when these patients complete
      the first week course of treatment. PCR-RFLP method will be used to detect genotype of
      CYP2C19 polymorphism using the genomic DNA extracted from the whole blood in all 130 treated
      patients. The genotyping results will be correlated with the H. pylori eradication rate and
      intragastric pH value.

      The equivalence of demographic information among various treatment groups or genotypes will
      be revealed by chi-square independence test, t-test, one-way ANOVA, or Kruskal-Wallis test.
      The above statistical methods as well as Mann-Whitney test will be also used to analyze
      clinical outcome. Confidence intervals for eradication rates will be computed by plus-four
      method. Multiple logistic regression will be used to explore the predictor of the eradication
      outcome. Multiple regression will be used to explore the predictor of the intragastric
      acidity. A p-value less than 0.05 will be considered statistically significant.
    

Intervention name(s): omeprazole plus amoxicillin; omeprazole plus amoxicillin; omeprazole plus amoxicillin; omeprazole plus amoxicillin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention MeSH terms: Amoxicillin; Omeprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Investigator)
Primary purpose: Treatment
Keywords: Helicobacter pylori; CYP2C19 genotype; intragastric pH; dual therapy; antibiotic resistance