NXY-059 for acute ischemic stroke.

@article{Lees2006NXY059FA,
  title={NXY-059 for acute ischemic stroke.},
  author={Kennedy R. Lees and Justin A. Zivin and Tim J. Ashwood and Antoni D{\'a}valos and Stephen M. Davis and Hans Christoph Diener and James Charles Grotta and Patrick D. Lyden and Ashfaq Shuaib and Hans-goran H{\aa}rdemark and Warren W. Wasiewski},
  journal={The New England journal of medicine},
  year={2006},
  volume={354 6},
  pages={
          588-600
        }
}
BACKGROUND NXY-059 is a free-radical-trapping agent that is neuroprotective in animal models of stroke. We tested whether it would reduce disability in humans after acute ischemic stroke. METHODS We conducted a randomized, double-blind, placebo-controlled trial involving 1722 patients with acute ischemic stroke who were randomly assigned to receive a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours after the onset of the stroke. The primary outcome was disability at 90 days… 

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References

SHOWING 1-10 OF 34 REFERENCES
Tolerability of NXY-059 at Higher Target Concentrations in Patients With Acute Stroke
TLDR
NXY-059 was well tolerated in patients with an acute stroke at and above concentrations shown to be neuroprotective in an animal model when initiated 4 hours after onset of permanent focal ischemia.
Tolerability and Pharmacokinetics of the Nitrone NXY-059 in Patients With Acute Stroke
TLDR
NXY-059 was well tolerated in patients with an acute stroke, and the testing of higher doses in future trials may be justified.
NXY-059, a Free Radical–Trapping Agent, Substantially Lessens the Functional Disability Resulting From Cerebral Ischemia in a Primate Species
TLDR
This novel drug has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species, and these findings provide considerable encouragement for the clinical development of NXY-059.
Functional and histological evidence for the protective effect of NXY-059 in a primate model of stroke when given 4 hours after occlusion.
TLDR
NXY-059 is an effective neuroprotective agent when administered 4 hours after pMCAO in a primate species, attenuating both motor and spatial neglect and substantially lessened the volume of cerebral damage.
Neuroprotective Effects of a Novel Nitrone, NXY-059, after Transient Focal Cerebral Ischemia in the Rat
TLDR
Studies of the transfer constant of [14C]NXY-059 showed that, in contrast to PBN, this more soluble nitrone penetrates the blood-brain barrier less extensively, suggesting that the delayed events leading to infarction may be influenced by reactions occurring at the blood–endothelial interface.
Effect of NXY‐059 on infarct volume after transient or permanent middle cerebral artery occlusion in the rat; studies on dose, plasma concentration and therapeutic time window
TLDR
The data demonstrate the substantial neuroprotective efficacy of N XY‐059 at plasma concentrations that can be achieved clinically and indicate that NXY‐059 also has a therapeutic window of opportunity that is clinically relevant.
Targeting Neuroprotection Clinical Trials to Ischemic Stroke Patients With Potential to Benefit From Therapy
TLDR
Targeting patients with potential to benefit enables a substantial sample size reduction without compromising statistical power or duration of recruitment, and informed use of prognostic data available acutely would help in identifying effective neuroprotective treatments.
Glycine Antagonist (GV150526) in Acute Stroke: A Multicentre, Double-Blind Placebo-Controlled Phase II Trial
TLDR
GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified, and results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV 150526.
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