A randomized efficacy trial of citicoline in patients with acute ischemic stroke.
OBJECTIVE
Citicoline (cytidine-5'-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 (n=127) with citicoline (n=267) (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) > or = 5 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 <8 (34% vs 22%; P<0.01). 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 > or = 95 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 > or = 8 found that citicoline-treated patients were more likely to have a full recovery (Barthel > or = 95): placebo 21%; citicoline 33%; P=0.05; whereas no difference was seen in patients with baseline 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 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.
Clark
W M
WM
Oregon Stroke Center, Oregon Health Sciences University, Portland 97201, USA. Clarkw@ohsu.edu
Williams
B J
BJ
Selzer
K A
KA
Zweifler
R M
RM
Sabounjian
L A
LA
Gammans
R E
RE
D000368:Aged; D000465:Algorithms; D003566:Cytidine Diphosphate Choline / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D016015:Logistic Models; D008297:Male; D018697:Nootropic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016017:Odds Ratio
D018697:Nootropic Agents; D003566:Cytidine Diphosphate Choline