Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area

Eur J Intern Med. 2016 Jul:32:84-90. doi: 10.1016/j.ejim.2016.04.011. Epub 2016 Apr 28.

Abstract

Background: Currently only a few studies compare sequential and concomitant non-bismuth Helicobacter pylori therapies referring to high antibiotic resistance populations.

Materials and methods: This multicenter prospective randomized clinical trial included 353 H. pylori positive, treatment naïve, patients. All patients had positive CLO-test and/or histology and culture. They received sequential (esomeprazole 40mg, amoxicillin 1g/bid for 5days, followed by 5days of esomeprazole 40mg, clarithromycin 500mg and metronidazole 500mg bid), or concomitant treatment (all drugs taken concomitantly bid for 10days). Eradication was confirmed by (13)C-urea breath test or histology 4-6weeks after treatment. Adverse events and adherence were evaluated.

Results: Allocated to concomitant were 175 (72F/103M, mean 52.3years, 38.3% smokers, 25.7% ulcer disease) and 178 (87F/91M, mean 52years, 31% smokers, 19.1% ulcer disease) patients to sequential treatment. There were 303/353 (85.8%) positive cultures, with the following resistances: 34% metronidazole, 27.7% clarithromycin, and 7.9% dual. Eradication rates were, respectively, 89.1% (156/175) vs. 78.7% (140/178) by intention to treat (p=0.01, 95% CI=2.7-18) and 93.4%(156/167) vs. 82.8% (140/169) per protocol (p=0.004, 95% CI=3.6-17.6). Overall, adherence was (98.9%, 95% CI=97-100). Eradication rates according to resistance were the following: dual susceptible strains 67/69 (97.1%), 62/67 (92%) (p=0.4), metronidazole single resistant 38/39 (97.4%), 31/39 (79.5%) (p=0.03, 95% CI=3.5-33), clarithromycin single resistant 25/28 (89.3%), 26/31 (83.9%) (p=0.8), and dual resistant 9/12 (75%), 4/11 (36.4%) (p=0.1) for concomitant and sequential regimens, respectively. Side effects were comparable among regimens, except from diarrhea being more frequent among patients treated with concomitant treatment.

Conclusions: Concomitant treatment eradication rate overcomes 90% per protocol and has a significant advantage over sequential therapy. This is probably due to its better efficacy on metronidazole resistant strains. Both regimens were well tolerated and safe.

Keywords: Clarithromycin resistance; Concomitant treatment; First line; H. pylori treatment; Metronidazole resistance; Sequential treatment.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Amoxicillin / administration & dosage*
  • Anti-Bacterial Agents / administration & dosage*
  • Biopsy
  • Breath Tests
  • Carbon Isotopes
  • Clarithromycin / administration & dosage*
  • Drug Resistance, Bacterial
  • Drug Therapy, Combination
  • Dyspepsia / drug therapy*
  • Dyspepsia / microbiology
  • Esomeprazole / administration & dosage*
  • Female
  • Helicobacter Infections / drug therapy*
  • Helicobacter Infections / metabolism
  • Helicobacter Infections / pathology
  • Helicobacter pylori
  • Humans
  • Male
  • Metronidazole / administration & dosage*
  • Middle Aged
  • Peptic Ulcer / drug therapy*
  • Peptic Ulcer / microbiology
  • Proton Pump Inhibitors / administration & dosage*
  • Pyloric Antrum / pathology
  • Urea / metabolism

Substances

  • Anti-Bacterial Agents
  • Carbon Isotopes
  • Proton Pump Inhibitors
  • Metronidazole
  • Amoxicillin
  • Urea
  • Clarithromycin
  • Esomeprazole