title: 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial.
abstract: BACKGROUND
  Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton-pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradication of Helicobacter pylori infection than are 5-day concomitant and 10-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses than do three-drug regimens and thus could be suitable for eradication programmes in low-resource settings. Few studies in Latin America have been done, where the burden of H pylori-associated diseases is high. We therefore did a randomised trial in Latin America comparing the effectiveness of four-drug regimens given concomitantly or sequentially with that of a standard 14-day regimen of triple therapy.
  
  
  METHODS
  Between September, 2009, and June, 2010, we did a randomised trial of empiric 14-day triple, 5-day concomitant, and 10-day sequential therapies for H pylori in seven Latin American sites: Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites). Participants aged 21-65 years who tested positive for H pylori by a urea breath test were randomly assigned by a central computer using a dynamic balancing procedure to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); 5 days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or 5 days of lansoprazole and amoxicillin followed by 5 days of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by urea breath test 6-8 weeks after randomisation. The trial was not masked. Our primary outcome was probablity of H pylori eradication. Our analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, registration number NCT01061437.
  
  
  RESULTS
  1463 participants aged 21-65 years were randomly allocated a treatment: 488 were treated with 14-day standard therapy, 489 with 5-day concomitant therapy, and 486 with 10-day sequential therapy. The probability of eradication with standard therapy was 82·2% (401 of 488), which was 8·6% higher (95% adjusted CI 2·6-14·5) than with concomitant therapy (73·6% [360 of 489]) and 5·6% higher (-0·04% to 11·6) than with sequential therapy (76·5% [372 of 486]). Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites.
  
  
  CONCLUSIONS
  Standard 14-day triple-drug therapy is preferable to 5-day concomitant or 10-day sequential four-drug regimens as empiric therapy for H pylori infection in diverse Latin American populations.
  
  
  BACKGROUND
  Bill & Melinda Gates Foundation, US National Institutes of Health.
authors.affiliation: SWOG Statistical Center, Cancer Research and Biostatistics, Seattle, WA 98101-1468, USA. e.r.greenberg@dartmouth.edu
authors.forename: E Robert
authors.initials: ER
authors.lastname: Greenberg
authors.forename: Garnet L
authors.initials: GL
authors.lastname: Anderson
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Morgan
authors.forename: Javier
authors.initials: J
authors.lastname: Torres
authors.forename: William D
authors.initials: WD
authors.lastname: Chey
authors.forename: Luis Eduardo
authors.initials: LE
authors.lastname: Bravo
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Dominguez
authors.forename: Catterina
authors.initials: C
authors.lastname: Ferreccio
authors.forename: Rolando
authors.initials: R
authors.lastname: Herrero
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Lazcano-Ponce
authors.forename: María Mercedes
authors.initials: MM
authors.lastname: Meza-Montenegro
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Peña
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Peña
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salazar-Martínez
authors.forename: Pelayo
authors.initials: P
authors.lastname: Correa
authors.forename: María Elena
authors.initials: ME
authors.lastname: Martínez
authors.forename: Manuel
authors.initials: M
authors.lastname: Valdivieso
authors.forename: Gary E
authors.initials: GE
authors.lastname: Goodman
authors.forename: John J
authors.initials: JJ
authors.lastname: Crowley
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Baker
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000008:administration & dosage*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D001944:Breath Tests; D017291:Clarithromycin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D016481:Helicobacter Infections / Q000175:diagnosis / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects; D006801:Humans; D064747:Lansoprazole; D007843:Latin America; D008297:Male; D008795:Metronidazole / Q000008:administration & dosage*; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000008:administration & dosage*; D013997:Time Factors; D016896:Treatment Outcome; D014508:Urea / Q000378:metabolism
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D008795:Metronidazole; D000658:Amoxicillin; D014508:Urea; D017291:Clarithromycin