Mark J. Alberts, MD
Does citicoline improve recovery after moderate-to-severe acute ischemic stroke in adults?
Randomized placebo-controlled trial (International Citicoline Trial on acUte Stroke [ICTUS]). ClinicalTrials.gov NCT00331890.
Blinded* (patients, caregivers, clinicians, investigators, outcome assessors, data managers, and steering committee).
59 university hospitals in Germany, Portugal, and Spain.
2298 adults ≥ 18 years of age (mean age 73 y, 50% women) who had acute ischemic stroke referable to the middle cerebral artery territory with compatible neuroimaging; symptom onset within 24 hours; score ≥ 8 on the National Institutes of Health Stroke Scale (NIHSS), of which ≥ 2 points were from sections 5 and 6; prestroke modified Rankin score of 0 or 1; ≤ 12 hours between hospital admission and randomization; and < 1 hour between randomization and first dose of study drug.
Citicoline, 1000 mg every 12 hours (n = 1148), or placebo (n = 1150), for 6 weeks. Citicoline was administered intravenously for the first 3 days and orally from day 4 through week 6.
Primary outcome was recovery (global test combining favorable scores on each of the modified Rankin score [0 to 1], NIHSS [0 to 1], and Barthel index [95 to 100]) at 90 days. Secondary outcomes were the individual components of the primary outcome. Safety outcomes included mortality and serious adverse events. The study was designed to detect an odds ratio of 1.26 in favor of citicoline (80% power, 2-sided α = 0.05).
1697 patients (74%) completed follow-up at 90 days; 466 (20%) died before 90-day follow-up and were assigned failing scores on all 3 tests comprising the primary outcome (intention-to-treat analysis).
Enrollment was stopped for futility. At 90 days, citicoline and placebo groups did not differ for recovery (or the 3 component tests), mortality, or serious adverse events (Table).
Citicoline did not improve recovery at 90 days after moderate-to-severe acute ischemic stroke.
Citicoline vs placebo in adults with moderate-to-severe acute ischemic stroke†
†NIHSS = National Institutes of Health Stroke Scale; NR = not reported; NS = not significant; RBR = relative benefit reduction; other abbreviations defined in Glossary. Analysis based on 2298 patients, with failing scores assigned to 466 patients who died and last outcome carried forward for 136 patients. RBI, RBR, and associated CIs calculated from odds ratios and placebo event rates in article. RRR and CI calculated from event rates in article
‡Modified Rankin scale 0 to 1, NIHSS 0 to 1, and Barthel index ≥ 95. Analysis adjusted for sequential design, minimization factors, and center.
§Lower scores indicate less disability in daily activities.
||Lower scores indicate lower stroke severity.
¶Higher scores indicate better performance in activities of daily living.
Alberts MJ. Citicoline did not improve recovery at 90 days after moderate-to-severe acute ischemic stroke. Ann Intern Med. ;157:JC3–13. doi: 10.7326/0003-4819-157-6-201209180-02013
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Published: Ann Intern Med. 2012;157(6):JC3-13.
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