Randomized controlled trial of clarithromycin and ethambutol in the treatment of Crohn's disease

Background: A mycobacterial infection may be the cause of Crohn's disease in some patients. Measurement of intestinal permeability may identify Crohn's disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury. Aim: To assess the effect of 3 months of clarithromycin and ethambutol on the disease activity and intestinal permeability in patients with Crohn's disease at high risk of relapse. Methods: Patients with Crohn's disease, with a lactulose-mannitol permeability test above 0.03, were randomly assigned to receive either clarithromycin. 500 mg twice daily, and ethambutol, 15 mg/kg daily, or identically appearing placebo for 3 months in addition to their regular therapy. The Harvey-Bradshaw index and the lactulose-mannitol test were assessed in a blind fashion every 3 months for 12 months. Results: Thirty-one patients were randomized to receive either drugs (n = 15) or placebo (n = 16). The groups were similar in age, sex, duration of disease, location of disease, past complications and disease severity. Specifically, there was no difference between the drug or placebo groups in the mean Harvey-Bradshaw index (4.8 vs. 4.4), number with active disease (33% vs. 44%) and mean lactulose-mannitol test (0.06 vs. 0.10). During the 12-month follow-up period, there were no consistent, statistically significant differences in the mean Harvey-Bradshaw index or lactulose-mannitol test between treatment and placebo groups. Individual patients showed either improvement or worsening of these indices, but these were not related to study medication. Specifically, no 'cures' were noted with anti-mycobacterial treatment. Conclusions: Three months of treatment with clarithromycin and ethambutol does not benefit Crohn's disease patients who are receiving standard medical therapy.