Oral citicoline in acute ischemic stroke: An individual patient data pooling analysis of clinical trials

Antoni Dávalos, José Castillo, José Álvarez-Sabín, Julio J. Secades, Joan Mercadal, Sonia López, Erik Cobo, Steven Warach, David Sherman, Wayne M. Clark, Rafael Lozano

Research output: Contribution to journalArticlepeer-review

191 Scopus citations


Background and Purpose - No single neuroprotective agent has been shown to influence outcome after acute stroke. Citicoline has been studied worldwide in many clinical trials with positive findings, but only I trial has obtained significant results in the primary efficacy variables. Our objective was to evaluate the effects of oral citicoline in patients with acute ischemic stroke by a data pooling analysis of clinical trials. The primary efficacy end point chosen was the common evaluation of recovery, combining National Institutes of Health Stroke Scale ≤ 1, modified Rankin Scale score ≤1, and Barthel Index ≥95 at 3 months using the generalized estimating equations analysis. Methods - A systematic search of all prospective, randomized, placebo-controlled, double-blind clinical trials with oral citicoline (MEDLINE, Cochrane, and Ferrer Group bibliographic databases) was undertaken. Individual patient data were extracted from each study and pooled in a single data file. The main inclusion criteria included compatible neuroimaging with ischemic stroke, National Institutes of Health Stroke Scale ≥8, and prior modified Rankin Scale score ≤1. Four clinical trials using various doses of oral citicoline (500, 1000, and 2000 mg) were identified. Results - Of 1652 randomized patients, 1372 fulfilled the inclusion criteria (583 received placebo, 789 received citicoline). Recovery at 3 months was 25.2% in citicoline-treated patients and 20.2% in placebo-treated patients (odds ratio [OR], 1.33; 95% CI, 1.10 to 1.62; P=0.0034). The dose showing the largest difference with placebo was 2000 mg, with 27.9% of patients achieving recovery (OR, 1.38; 95% CI, 1.10 to 1.72; P=0.0043). The overall safety of citicoline was similar to placebo. Conclusions - Treatment with oral citicoline within the first 24 hours after onset in patients with moderate to severe stroke increases the probability of complete recovery at 3 months.

Original languageEnglish (US)
Pages (from-to)2850-2857
Number of pages8
Issue number12
StatePublished - Dec 1 2002


  • Cytidine diphosphate choline
  • Neuroprotection
  • Stroke, acute
  • Stroke, ischemic

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing


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