A randomized, double-blind, placebo controlled-trial of triflusal in mild cognitive impairment: the TRIMCI study.

BACKGROUND

Amnestic mild cognitive impairment represents, in many cases, the earliest clinical phases of Alzheimer disease. Anti-inflammatory agents have epidemiologic support as drugs potentially beneficial in Alzheimer disease. In vivo studies have shown that Triflusal and its active metabolite 2-hydroxy-4-trifluoromethyl-benzoic acid have potent anti-inflammatory actions in the central nervous system.

METHODS

We conducted a randomized, double-blind, placebo-controlled trial of Triflusal in patients with amnestic mild cognitive impairment. Subjects were randomly assigned to receive 900 mg of Triflusal or placebo for 18 months. The primary outcome was a change in Cognitive subscale of the Alzheimer Disease Assessment Scale; conversion to dementia was a secondary outcome.

RESULTS

A slow rate of recruitment forced a premature cessation of the study. Two hundred and fifty-seven subjects were enrolled and followed-up for an average of 13 months. The significance level was not reached for the primary outcome even though a trend in favor of Triflusal was observed. However, there was a significant difference in the probability of progression to dementia of Alzheimer's type with a lower risk in the Triflusal compared with the placebo group (hazard ratio, 2.10; 95% confidence interval, 1.10-4.01; P=0.024).

CONCLUSIONS

In this study, Triflusal therapy was associated with a significant lower rate of conversion to dementia that is likely to be clinically relevant. Because the trial was prematurely halted, these results should be interpreted with caution and require further confirmation.