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

Stroke. 2002 Dec;33(12):2850-7. doi: 10.1161/01.str.0000038691.03334.71.

Abstract

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 1 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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Administration, Oral
  • Aged
  • Brain Ischemia / complications
  • Brain Ischemia / drug therapy*
  • Cytidine Diphosphate Choline / administration & dosage*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Neuroprotective Agents / administration & dosage*
  • Odds Ratio
  • Prospective Studies
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Recovery of Function / drug effects
  • Severity of Illness Index
  • Stroke / complications
  • Stroke / drug therapy*
  • Time Factors
  • Treatment Outcome

Substances

  • Neuroprotective Agents
  • Cytidine Diphosphate Choline