title: Randomized clinical trial comparing ten day concomitant and sequential therapies for Helicobacter pylori eradication in a high clarithromycin resistance area.
abstract: BACKGROUND
  Currently only a few studies compare sequential and concomitant non-bismuth Helicobacter pylori therapies referring to high antibiotic resistance populations.
  
  
  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.
authors.affiliation: GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece. Electronic address: georgpap@ath.forthnet.gr.
authors.forename: Sotirios D
authors.initials: SD
authors.lastname: Georgopoulos
authors.affiliation: GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece.
authors.forename: Elias
authors.initials: E
authors.lastname: Xirouchakis
authors.affiliation: Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Martinez-Gonzales
authors.affiliation: Gastroenterology Department, Alexandra General Hospital, Athens, Greece.
authors.forename: Evanthia
authors.initials: E
authors.lastname: Zampeli
authors.affiliation: Gastrenterology Department, Central Clinic of Athens, Athens, Greece.
authors.forename: Elias
authors.initials: E
authors.lastname: Grivas
authors.affiliation: Department of Histopathology, Athens Medical, Amaroussion Hospital, Athens, Greece.
authors.forename: Charikleia
authors.initials: C
authors.lastname: Spiliadi
authors.affiliation: Department of Histopathology, Alexandra General Hospital, Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sotiropoulou
authors.affiliation: Department of Histopathology, Metropolitan Hospital, Athens, Greece.
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Petraki
authors.affiliation: GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece.
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Zografos
authors.affiliation: GI and Hepatology Department, Athens Medical, Paleo Faliron Hospital, 36 Areos str., 175 62 Athens, Greece.
authors.forename: Fotini
authors.initials: F
authors.lastname: Laoudi
authors.affiliation: Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Dionysios
authors.initials: D
authors.lastname: Sgouras
authors.affiliation: Laboratory of Medical Microbiology, Hellenic Pasteur Institute, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Mentis
authors.affiliation: Gastrenterology Department, Central Clinic of Athens, Athens, Greece.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kasapidis
authors.affiliation: Gastroenterology Department, Alexandra General Hospital, Athens, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Michopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001706:Biopsy; D001944:Breath Tests; D002247:Carbon Isotopes; D017291:Clarithromycin / Q000008:administration & dosage*; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D004415:Dyspepsia / Q000188:drug therapy* / Q000382:microbiology; D064098:Esomeprazole / Q000008:administration & dosage*; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage*; D008875:Middle Aged; D010437:Peptic Ulcer / Q000188:drug therapy* / Q000382:microbiology; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D011706:Pyloric Antrum / Q000473:pathology; D014508:Urea / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002247:Carbon Isotopes; D054328:Proton Pump Inhibitors; D008795:Metronidazole; D000658:Amoxicillin; D014508:Urea; D017291:Clarithromycin; D064098:Esomeprazole
keywords: Clarithromycin resistance; Concomitant treatment; First line; H. pylori treatment; Metronidazole resistance; Sequential treatment