A phase III randomized efficacy trial of 2000 mg citicoline in acute ischemic stroke patients

Background: Citicoline may reduce CNS ischemic injury by stabilizing cell m embranes and reducing free radical generation. Previous safety and efficacy trials in patients who have had acute strokes suggested that citicoline ma y improve neurologic outcome with minimal side effects. Objective: To deter mine the safety and efficacy of citicoline treatment in acute stroke patien ts. Methods: An 118-center, randomized, double-blind, efficacy trial in 899 patients compared placebo (n = 446) with citicoline (n = 453) (1000 mg PO twice a day) for 6 weeks, with a 6-week post-treatment follow-up period. Pa tients with acute (less than or equal to 24 hours) ischemic strokes clinica lly thought to be in the middle cerebral artery territory with NIH Stroke S cale (NIHSS) scores greater than or equal to8 were enrolled. Results: Mean time to treatment was 13 hours for both groups and mean age was 67 years fo r those receiving placebo and 68 years for those receiving citicoline. Mean baseline NIHSS scores were 14.5 for placebo and 13.9 for citicoline (p = 0 .06); medians were 14 for placebo and 13 for citicoline (p = 0.04). The inc idence and type of side effects were similar between the groups. There were no between-group differences on the planned primary analysis, percent of p atients with a greater than or equal to7-point NIHSS score change at 90 day s (placebo 51%, citicoline 52%). There were no between-group differences on the other planned secondary analyses at 90 days, including mortality. Howe ver, post hoc analyses using standard "excellent recovery" measures suggest ed a possible treatment effect on the modified Rankin 0 or 1 (last observat ion carried forward: placebo 20%, citicoline 26%; p = 0.025) as well as a g lobal outcome statistic. Conclusions: Citicoline was safe but ineffective i n 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.