No abstract

Citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke as measured by the planned analyses. Post hoc analyses suggest that a modest treatment effect may have been seen if more traditional analyses had been used.

Background and Purpose-Citicoline (cytidine-5Ј-diphosphocholine; CDP-choline) may reduce central nervous system ischemic injury by stabilizing cell membranes and reducing free radical generation. A previous dose-comparison trial 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, efficacy trial in 394 patients comparing placebo (nϭ127) with citicoline (nϭ267) (500 mg po daily) for 6 weeks, with a 6-week posttreatment follow-up period. Patients with acute (24 hours) ischemic strokes clinically assessed to be in the middle cerebral artery territory with National Institutes of Health Stroke Scale (NIHSS) Ն5 were enrolled. Results-Mean time to treatment was 12 hours, and mean age was 71 for placebo and 70 for citicoline. Although mean baseline NIHSS were similar for both groups, there was a higher percentage of placebo patients with NIHSS Ͻ8 (34% vs 22%; PϽ0.01). The incidence and type of side effects were similar between the groups. The planned primary analysis (logistic regression: 5 categories Barthel) failed the proportional odds assumption and was rendered unreliable. There were no between-group differences seen on the planned secondary assessment analyses at 90 days, including the Barthel Index Ն95 at 12 weeks (last observation carried forward: placebo 40%; citicoline 40%) or mortality rate (placebo 18%; citicoline 17%). However, post hoc analyses in a subgroup of patients with baseline NIHSS Ն8 found that citicoline-treated patients were more likely to have a full recovery (Barthel Ն95): placebo 21%; citicoline 33%; Pϭ0.05; whereas no difference was seen in patients with baseline NIHSSϽ8 (placebo 77%; citicoline 69%; PϾ0.1. Conclusions-The results of this study indicate that citicoline was safe but ineffective in improving the outcome of patients with acute ischemic stroke who were enrolled in this trial. Post hoc analyses indicate that there may be a subgroup of patients with moderate to severe strokes who would benefit. (Stroke. 1999;30:2592-2597.)

IUSS is a validated patient reported measure of urgency severity for collecting event specific information in the context of a clinical trial.