Published Online
on June 14, 2007

A more recent version of this article appeared on August 1, 2007

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Submitted on September 11, 2006
Revised on January 10, 2007
Accepted on February 14, 2007

Safety and Tolerability of NXY-059 for Acute Intracerebral Hemorrhage. The CHANT Trial

Patrick D. Lyden MD^*; Ashfaq Shuaib MD; Kennedy R. Lees MD; Antoni Davalos MD; Stephen M. Davis MD; Hans-Christoph Diener MD; James C. Grotta MD; Tim J. Ashwood PhD; Hans-Goren Hardemark MD; Hannah H. Svensson MSc; Larry Rodichok MD; Warren W. Wasiewski MD; Gabrielle Åhlberg MD; for the CHANT Trial Investigators

From the UCSD Stroke Center and Department of Veterans Affairs Medical Center (P.D.L.), San Diego, Calif; the University of Alberta (A.S.), Canada; the Acute Stroke Unit & Cerebrovascular Clinic (K.R.L.), University Department of Medicine & Therapeutics, Gardiner Institute, Western Infirmary, Glasgow, UK; the Department of Neurosciences (A.D.), Hospital Universitari Germans Trias i Pujol, Universitat Autónoma de Barcelona, Spain; the Department of Neurology (S.M.D.), Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia; the Department of Neurology (H.C.D.), University Duisburg-Essen, Essen, Germany; the Department of Neurology (J.C.G.), University of Texas Medical School-Houston, Tex; AstraZeneca R&D Södertälje (T.J.A., H.G.H., H.H.S., G.A.), Södertälje, Sweden; and AstraZeneca L. P. (L.R., W.W.W.), Del.

^* To whom correspondence should be addressed. E-mail: Plyden{at}ucsd.edu.

Background and Purpose--NXY-059 is a free radical-trapping neuroprotectant developed for use in acute ischemic stroke. To facilitate prompt administration of treatment, potentially before neuroimaging, we investigated the safety of NXY-059 in patients with intracerebral hemorrhage (ICH).

Methods--We randomized 607 patients within 6 hours of acute ICH to receive 2270 mg intravenous NXY-059 over 1 hour and then up to 960 mg/h over 71 hours, or matching placebo, in addition to standard care. The primary outcome was safety: the mortality and the frequency of adverse events, and the change from baseline for a variety of serum, imaging, and electrophysiological measurements. We also studied the overall distribution of disability scores on the modified Rankin Scale (mRS) and the Barthel index.

Results--We treated 300 patients with NXY-059 and 303 with placebo. Treatment groups were well matched for prognostic variables including Glasgow Coma Scale, risk factors, and age. The mean National Institute of Health Stroke Scale score on admission was 14 in both groups. The baseline hemorrhage volume was 22.4±20.1 mL in the NXY-059 group and 23.3±22.8 mL in the placebo group (mean±SD). Most hemorrhages were related to hypertension or anticoagulant use. Mortality was similar in both groups: 20.3% for NXY-059 and 19.8% for placebo-treated patients. The proportion of patients who experienced an adverse event was the same for both groups, whereas for serious adverse events the proportion was slightly higher in the NXY-059 group. However, no pattern emerged to indicate a safety concern. Serum potassium fell transiently in both groups, lower in the NXY-059 group. There were no differences in 3-month function, disability, or neurological deficit scores. The odds ratio for an improved outcome in 3-month mRS scores in the NXY-059 group was 1.01 (95% CI 0.75, 1.35).

Conclusions--NXY-059 given within 6 hours of acute ICH has a good safety and tolerability profile, with no adverse effect on important clinical outcomes.

Key words: acute care • clinical trials • free radical scavengers • neuroprotectants • neuroprotection • neuroprotective agents • stroke management

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