Objective: To review available literature on the pharmacology, pharmacokinetics, efficacy, and tolerability of NXY-059, an investigational agent with a potential role in the treatment of acute stroke.

Data sources: Information was obtained from a MEDLINE search (1966-February 2006) of English-language literature utilizing the following search terms: NXY-059, cerovive, nitrones, neuroprotection, free radical trapper, and secondary neurologic injury.

Study selection and data extraction: Data from animal and human trials were evaluated to summarize the mechanism of action, efficacy, and safety of NXY-059. All published and unpublished trials and abstracts citing NXY-059 were selected.

Data synthesis: NXY-059 is an intravenous, nitrone-based, free radical trapping agent in Phase III trials for treatment of acute stroke. In various animal models, NXY-059 has shown reductions in infarct volume and neurologic deficits. Pharmacokinetic studies indicate that NXY-059 displays a predictable pharmacokinetic profile and primarily undergoes renal elimination. Results from 2 Phase II clinical trials showed favorable results for the safety and tolerability of the drug. A recent analysis of one of the Phase III trials showed a statistically significant reduction in the primary outcome of disability after acute stroke in patients who received NXY-059 compared with placebo.

Conclusions: NXY-059 is a novel agent undergoing worldwide Phase III trials. Initial safety and efficacy data have not revealed any serious adverse events requiring special monitoring and/or precautions, with the exception of drug accumulation in patients with renal insufficiency. The potential benefit of this agent can change the current management algorithm for acute stroke and may represent significant advancement for the care of these patients.