title: Reverse sequential therapy achieves a similar eradication rate as standard sequential therapy for Helicobacter pylori eradication: a randomized controlled trial.
abstract: OBJECTIVE
  Sequential therapy is a two-step therapy achieving a promising eradication rate for Helicobacter pylori infection. The rationale of sequential method has been proposed that amoxicillin weakens bacterial cell walls in the initial phase of treatment, preventing the development of drug efflux channels for clarithromycin and metronidazole used in the second phase. The aim of this prospective, randomized, controlled study was to investigate whether the efficacy of reverse sequential therapy was noninferior to sequential therapy in the treatment of H. pylori infection.
  
  
  METHODS
  From January 2009 to December 2010, consecutive H. pylori-infected patients were randomly assigned to receive either sequential therapy (a 5-day dual therapy with pantoprazole plus amoxicillin, followed by a 5-day triple therapy with pantoprazole plus clarithromycin and metronidazole) or reverse sequential therapy (a 5-day triple therapy with pantoprazole plus clarithromycin and metronidazole, followed by a 5-day dual therapy with pantoprazole plus amoxicillin). H. pylori status was examined 6 weeks after the end of treatment by rapid urease and histology or urea breath test.
  
  
  RESULTS
  One hundred and twenty-two H. pylori-infected participants were randomized to receive sequential (n = 60) or reverse sequential therapy (n = 62). The eradication rates, by intention-to-treat analysis, were similar: 91.9% (95% confidence interval (CI): 85.1-98.7%) for sequential therapy and 96.7% (95% CI: 92.2-101.2%) for reverse sequential therapy (p = .44). Per-protocol analysis also showed similar results: 91.8% (95% CI: 84.9-98.7%) for sequential group and 96.7% (95% CI: 92.2-101.2%) for reverse sequential therapy (p = .43). The two treatments exhibited comparable frequencies of adverse events (11.3% vs 6.7%, respectively) and drug compliance (98.4% vs 100%, respectively). The overall resistance rates of antibiotics were clarithromycin 10.5%, amoxicillin 0%, and metronidazole 44.2% of patients, respectively. The dual resistance rate of clarithromycin and metronidazole was 4.2%. Both therapies achieved a high eradication rate for clarithromycin-resistant strains (100% vs 100%, respectively) and metronidazole-resistant strains (81.8% vs 95%, respectively) by intention-to-treat analysis.
  
  
  CONCLUSIONS
  Ten-day reverse sequential therapy and standard sequential therapy are equally effective for H. Pylori eradication. The finding indicates that the sequence of antibiotics administered in sequential therapy does not influence the efficacy of the treatment.
authors.affiliation: Division of Gastroenterology, Department of internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan; Cheng Shiu University, Kaohsiung, Taiwan.
authors.forename: Feng-Woei
authors.initials: FW
authors.lastname: Tsay
authors.forename: Deng-Chyang
authors.initials: DC
authors.lastname: Wu
authors.forename: Sung-Shuo
authors.initials: SS
authors.lastname: Kao
authors.forename: Tzung-Jium
authors.initials: TJ
authors.lastname: Tsai
authors.forename: Kwok-Hung
authors.initials: KH
authors.lastname: Lai
authors.forename: Jin-Shiung
authors.initials: JS
authors.lastname: Cheng
authors.forename: Hoi-Hung
authors.initials: HH
authors.lastname: Chan
authors.forename: Huay-Min
authors.initials: HM
authors.lastname: Wang
authors.forename: Wei-Lun
authors.initials: WL
authors.lastname: Tsai
authors.forename: Hui-Hwa
authors.initials: HH
authors.lastname: Tseng
authors.forename: Nan-Jin
authors.initials: NJ
authors.lastname: Peng
authors.forename: Ping-I
authors.initials: PI
authors.lastname: Hsu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D017291:Clarithromycin; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy*; D016480:Helicobacter pylori / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D008795:Metronidazole; D000658:Amoxicillin; D017291:Clarithromycin
keywords: Helicobacter pylori; Sequential therapy; reverse sequential therapy