A randomized efficacy trial of citicoline in patients with acute ischemic stroke

Background and Purpose-Citicoline (cytidine-5'-diphosphocholine; CDP-cholin e) may reduce central nervous system ischemic injury by stabilizing cell me mbranes and reducing free radical generation. A previous dose-comparison tr ial in patients with acute stroke found that 500 mg of citicoline appeared to improve neurological outcome with minimal side effects. Methods-The current trial was a 33-center, randomized, double-blind, effica cy trial in 394 patients comparing placebo (n = 127) with citicoline (n = 2 67) (500 mg po daily) for 6 weeks, with a 6-week posttreatment follow-up pe riod. Patients with acute (24 hours) ischemic strokes clinically assessed t o be in the middle cerebral artery territory with National Institutes of He alth Stroke Scale (NIHSS) greater than or equal to 5 were enrolled. Results-Mean time to treatment was 12 hours, and mean age was 71 for placeb o and 70 for citicoline, Although mean baseline NIHSS were similar for both groups, there was a higher percentage of placebo patients with NIHSS <8 (3 4% vs 22%; P<0.01). The incidence and type of side effects were similar bet ween the groups. The planned primary analysis (logistic regression: 5 categ ories Barthel) failed the proportional odds assumption and was rendered unr eliable. There were no between-group differences seen on the planned second ary assessment analyses at 90 days, including the Barthel Index greater tha n or equal to 95 at 12 weeks (last observation carried forward: placebo 40% ; citicoline 30%) or mortality rate (placebo 18%; citicoline 17%). However, post hoc analyses in a subgroup of patients with baseline NIHSS greater th an or equal to 8 found that citicoline-treated patients were more likely to have a full recovery (Barthel greater than or equal to 95): placebo 21%; c iticoline 33%; P=0.05; whereas no difference was seen in patients with base line NIHSS<8 (placebo 77%; citicoline 69%: P>0.1. Conclusions-The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic strok e who were enrolled in this trial. Post hoc analyses indicate that there ma y be a subgroup of patients with moderate to severe strokes who would benef it.