More neuroprotection disappointment for acute stroke
MedWire News: The International Citicoline Trial on acUte Stroke (ICTUS) investigators have reported negative results, representing another failed attempt to provide neuroprotection in patients with acute stroke.
Patients randomly assigned to receive citicoline did no better than those given placebo on a global outcome score combining their responses on the Barthel Index, the modified Rankin Scale, and the National Institutes of Health Stroke Scale.
Citicoline previously showed efficacy in experimental stroke, and a meta-analysis of trials including nearly 2000 patients suggested a beneficial effect of oral citicoline in stroke patients.
Patients given citicoline in ICTUS received it as an intravenous infusion of 1000 mg over 12 hours for the first 3 days of treatment followed by the same dose orally through week 6. Patients in the control group received matching placebo treatment. At the point at which the trial was halted (having crossed a prespecified boundary), it had recruited 2298 patients. The patients were treated within 24 hours of symptom onset, with a median time to treatment of 7 hours.
Besides not affecting the global outcome score, citicoline treatment also failed to increase the rate of favorable outcomes on any individual scale, and had no effect in shift (ordinal) analysis of the modified Rankin Scale, either in the intention-to-treat or per-protocol populations.
However, there were no safety issues with citicoline, with no between-group differences in mortality, intracranial hemorrhage, or neurologic deterioration, Antoni Dávalos (Hospital Universitari Germans Trias i Pujol in Barcelona, Spain) told delegates at the European Stroke Conference in Lisbon, Portugal.
Commenting on the study to MedWire, Michael Hennerici (University of Heidelberg, Germany), who was not involved in the research, said that the results are "disappointing but not unexpected," given that more than 10 years of study of multiple putative neuroprotectants have failed to show benefits in patients.
He noted that the lengthy time to treatment could have contributed to the overall negative effect, and suggested that a more effective neuroprotective approach might be to treat patients while they are being considered for thrombolysis, so patients potentially benefit from two treatments.
International Stroke Trial-3 investigator Richard Lindley (University of Sydney, Australia) added that retrospective analyses of neuroprotectant studies in animal have revealed many flaws, and that the only treatment to consistently demonstrate benefits is hypothermia.
A major study of hypothermia in stroke patients (EuroHYP) is currently in progress.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012
By Eleanor McDermid