BACKGROUND & AIMS: Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol, and calcium carbonate could prevent colorectal adenoma recurrence.

METHODS: We included 1107 patients with 1 or more sporadic adenoma(s) removed from the colon or rectum at centers in Europe, Russia, or the United States, from 2004 through 2010. Inclusion criteria were 1 adenoma greater than 1 cm in diameter, more than 1 adenoma of any size, or an adenoma of any size and first-degree relatives with colorectal cancer. Subjects were assigned randomly to groups given 0.5 μg calcitriol, 75 mg acetylsalicylic acid, and 1250 mg calcium carbonate (n = 209), or placebo (n = 218), each day for 3 years. The primary outcome was adenoma recurrence assessed by colonoscopy after 3 years. Secondary outcomes were the proportion of patients with advanced adenomas, the total number of colorectal adenomas, and adenoma size and features.

RESULTS: The trial was stopped in October 2010 because of futility. In this analysis, we found no differences between groups in the rate of recurrence (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.61-1.48), adverse effects, or secondary outcomes. Subgroup analyses indicated that the treatment effects may be influenced by smoking status (nonsmokers OR, 0.65; 95% CI, 0.26-1.22 vs current smokers OR, 1.70; 95% CI, 0.70-4.09; P value interaction < .05). However, the overall interaction was not significant.

CONCLUSIONS: In a prospective study, the combination of calcitriol, aspirin, and calcium carbonate did not prevent recurrence of colorectal adenomas over a 3-year period. The negative results might be owing to the effects of smoking or low doses of the tested agents. Clinicaltrials.gov number: NCT00486512.