(Stroke. 1999;30:2592.)
© 1999 American Heart Association, Inc.
Original Contributions |
A Randomized Efficacy Trial of Citicoline in Patients With Acute Ischemic Stroke
From Oregon Stroke Center, Oregon Health Sciences University, Portland, Ore (W.M.C.); Forsyth Memorial Hospital, Winston Salem, NC (B.J.W.); Scripps Memorial Hospital, La Jolla, Calif (K.A.S.); University of South Alabama, Mobile (L.A.S., R.E.G.); and Interneuron Pharmaceuticals, Inc, Lexington, Mass.
Correspondence to Dr Wayne M. Clark, Oregon Stroke Center UHS 44, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201. E-mail Clarkw{at}ohsu.edu
Background and Purpose—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) 
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 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 8 found that citicoline-treated patients were more
likely to have a full recovery (Barthel 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.
Key Words: citicoline • stroke • treatment
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