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Addition of Metronidazole to Azathioprine for the Prevention of Postoperative Recurrence of Crohn’s Disease: A Randomized, Double-Blind, Placebo-Controlled Trial

Mañosa, Míriam PhD, MD*,†; Cabré, Eduard PhD, MD*,†; Bernal, Isabel MD*; Esteve, Maria PhD, MD†,‡; Garcia-Planella, Esther MD§; Ricart, Elena PhD, MD†,§; Peñalva, Mireia MD; Cortes, Xavier MD; Boix, Jaume MD*; Piñol, Marta MD*; Gassull, Miquel A. PhD, MD*; Domènech, Eugeni PhD, MD*,†

doi: 10.1097/MIB.0b013e31828ef13f
Original Clinical Articles

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.

Article first published online 17 May 2013

*Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain;

Department of Gastroenterology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain;

Department of Gastroenterology, Hospital Mútua de Terrassa, Terrassa, Spain;

§Department of Gastroenterology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;

Department of Gastroenterology, Hospital de Bellvitge, L’Hospitalet de Llobregat, Spain; and

Department of Gastroenterology, Hospital de Sagunto, Sagunto, Spain.

Reprints: Míriam Mañosa, MD, PhD, IBD Unit, Gastroenterology Department, Hospital Universitari Germans Trias i Pujol, Ctra. del Canyet, s/n, 08916 Badalona, Spain (e-mail:

Support received from La Marató de TV3 Foundation.

The authors have no conflicts of interest to disclose.

Received December 21, 2012

Accepted January 30, 2013

© Crohn's & Colitis Foundation of America, Inc.
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