title: Addition of metronidazole to azathioprine for the prevention of postoperative recurrence of Crohn's disease: a randomized, double-blind, placebo-controlled trial.
abstract: BACKGROUND
  Endoscopic recurrence occurs in up to 80% of patients with Crohn's disease 1 year after intestinal resection. Imidazole antibiotics, thiopurines, and particularly their combination have proven efficacy in preventing endoscopic recurrence. The aim of the study was to compare the efficacy of the addition of metronidazole (for 3 months after the surgical treatment) to azathioprine for the prevention of postsurgical endoscopic recurrence.
  
  
  METHODS
  A pilot study was made of 50 patients with Crohn's disease undergoing intestinal resection with ileocolic anastomosis and treated with 2 to 2.5 mg/kg of azathioprine per day for 1 year. The patients were randomized to receive additional 15 to 20 mg/kg of metronidazole per day or placebo for the first 3 months (n = 25 per arm). Endoscopic assessment was performed 6 and 12 months after the surgical resection. The primary end point was the prevention of endoscopic recurrence as defined by a Rutgeerts score of <2 at 6 months. The initial sample size had an 80% statistical power in detecting an absolute risk reduction of ≥30%.
  
  
  RESULTS
  Endoscopic recurrence occurred in 28% and 44% of the patients at 6 months (P = 0.19) and in 36% and 56% (P = 0.15) at 12 months in the metronidazole and placebo groups, respectively. No statistically significant differences were found between the treatment groups regarding severe endoscopic recurrence (Rutgeerts score ≥ 3) at 6 and 12 months. Likewise, there were no differences in the rate of adverse events between the treatment groups.
  
  
  CONCLUSIONS
  The addition of metronidazole to azathioprine did not significantly reduce the risk of endoscopic recurrence beyond azathioprine alone in this study but does not worsen its safety profile.
authors.affiliation: Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. mmanosa.germanstrias@gencat.cat
authors.forename: Míriam
authors.initials: M
authors.lastname: Mañosa
authors.forename: Eduard
authors.initials: E
authors.lastname: Cabré
authors.forename: Isabel
authors.initials: I
authors.lastname: Bernal
authors.forename: Maria
authors.initials: M
authors.lastname: Esteve
authors.forename: Esther
authors.initials: E
authors.lastname: Garcia-Planella
authors.forename: Elena
authors.initials: E
authors.lastname: Ricart
authors.forename: Mireia
authors.initials: M
authors.lastname: Peñalva
authors.forename: Xavier
authors.initials: X
authors.lastname: Cortes
authors.forename: Jaume
authors.initials: J
authors.lastname: Boix
authors.forename: Marta
authors.initials: M
authors.lastname: Piñol
authors.forename: Miquel A
authors.initials: MA
authors.lastname: Gassull
authors.forename: Eugeni
authors.initials: E
authors.lastname: Domènech
mesh_terms: D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000150:complications / Q000601:surgery*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004724:Endoscopy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D010865:Pilot Projects; D011183:Postoperative Complications / Q000517:prevention & control*; D011379:Prognosis; D055502:Secondary Prevention; D055815:Young Adult
chemical_list: D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D008795:Metronidazole; D001379:Azathioprine