title: Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial.
abstract: BACKGROUND
  Helicobacter pylori is associated with benign and malignant diseases of the upper gastrointestinal tract, and increasing antibiotic resistance has made alternative treatments necessary. Our aim was to assess the efficacy and safety of a new, single-capsule treatment versus the gold standard for H pylori eradication.
  
  
  METHODS
  We did a randomised, open-label, non-inferiority, phase 3 trial in 39 sites in Europe, comparing the efficacy and safety of 10 days of quadruple therapy with omeprazole plus a single three-in-one capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline (quadruple therapy) versus 7 days of omeprazole, amoxicillin, and clarithromycin (standard therapy) in adults with recorded H pylori infection. Patients were randomly assigned treatment according to a predetermined list independently generated by Quintiles Canada (Ville St-Laurent, QC, Canada). Our study was designed as a non-inferiority trial but was powered to detect superiority. Our primary outcome was H pylori eradication, established by two negative (13)C urea breath tests at a minimum of 28 and 56 days after the end of treatment. Our assessment for non-inferiority was in the per-protocol population, with subsequent assessment for superiority in the intention-to-treat population (ie, all participants randomly assigned treatment). This study is registered with ClinicalTrials.gov, number NCT00669955.
  
  
  RESULTS
  12 participants were lost to follow-up and 101 were excluded from the per-protocol analysis. In the per-protocol population (n=339), the lower bound of the CI for treatment with quadruple therapy was greater than the pre-established non-inferiority margin of -10% (95% CI 15·1-32·3; p<0·0001). In the intention-to-treat population (n=440), eradication rates were 80% (174 of 218 participants) in the quadruple therapy group versus 55% (123 of 222) in the standard therapy group (p<0·0001). Safety profiles for both treatments were similar; main adverse events were gastrointestinal and CNS disorders.
  
  
  CONCLUSIONS
  Quadruple therapy should be considered for first-line treatment in view of the rising prevalence of clarithromycin-resistant H pylori, especially since quadruple therapy provides superior eradication with similar safety and tolerability to standard therapy.
  
  
  BACKGROUND
  Axcan Pharma Inc.
authors.affiliation: Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke-Universtität, Magdeburg, Germany. peter.malfertheiner@med.ovgu.de
authors.forename: Peter
authors.initials: P
authors.lastname: Malfertheiner
authors.forename: Franco
authors.initials: F
authors.lastname: Bazzoli
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Delchier
authors.forename: Krysztof
authors.initials: K
authors.lastname: Celiñski
authors.forename: Monique
authors.initials: M
authors.lastname: Giguère
authors.forename: Marc
authors.initials: M
authors.lastname: Rivière
authors.forename: Francis
authors.initials: F
authors.lastname: Mégraud
mesh_terms: D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001944:Breath Tests; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects; D004338:Drug Combinations; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000175:diagnosis / Q000188:drug therapy*; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009853:Omeprazole / Q000008:administration & dosage / Q000009:adverse effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects; D013607:Tablets; D013752:Tetracycline / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D004338:Drug Combinations; D009942:Organometallic Compounds; D013607:Tablets; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline; D017291:Clarithromycin; C002791:bismuth tripotassium dicitrate; D009853:Omeprazole