Article

Additional Outcomes and Subgroup Analyses of NXY-059 for Acute Ischemic Stroke in the SAINT I Trial

Acute Stroke Unit & Cerebrovascular Clinic, University Department of Medicine & Therapeutics, Gardiner Institute, Western Infirmary, 44 Church St, Glasgow, Scotland G11 6NT.
Stroke (Impact Factor: 5.72). 01/2007; 37(12):2970-8. DOI: 10.1161/01.STR.0000249410.91473.44
Source: PubMed

ABSTRACT

NXY-059 is a free radical-trapping neuroprotectant demonstrated to reduce disability from ischemic stroke. We conducted analyses on additional end points and sensitivity analyses to confirm our findings.
We randomized 1722 patients with acute ischemic stroke to a 72-hour infusion of placebo or intravenous NXY-059 within 6 hours of stroke onset. The primary outcome was disability at 90 days, as measured by the modified Rankin Scale (mRS), a 6-point scale ranging from 0 (no residual symptoms) to 5 (bed-bound, requiring constant care). Additional and exploratory analyses included mRS at 7 and 30 days; subgroup interactions with final mRS; assessments of activities of daily living by Barthel index; and National Institutes of Health Stroke Scale (NIHSS) neurological scores at 7 and 90 days.
NXY-059 significantly improved the distribution of the mRS disability score compared with placebo at 7, 30, and 90 days (Cochran-Mantel-Haenszel test P=0.002, 0.004, 0.038, respectively; 90-day common odds ratio 1.20; 95% CI, 1.01 to 1.42). The benefit was not attributable to any specific baseline characteristic, stratification variable or subgroup interaction. Neurological scores were improved at 7 days (odds ratio [OR], 1.46; 95% CI, 1.13, 1.89; P=0.003) and the Barthel index was improved at 7 and 30 days (OR, 1.55; 95% CI, 1.22, 1.98; P<0.0001; OR, 1.27; 95% CI, 1.01, 1.59; P=0.02).
NXY-059 within 6 hours of acute ischemic stroke significantly reduced disability. Benefit on neurological scores and activities of daily living was detectable early but not significant at 90 days; however, our trial was underpowered to measure effects on the neurological examination. The benefit on disability is not confounded by interactions and is supported by other outcome measures.

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    • "), CPI-1189 (Centaur [433] [434]), disufenton sodium (Cerovive, NXY-059, AstraZeneca, which was in Phase III clinical trials for the treatment of acute ischemic stroke [435] [436] [437] [438] [439] [440] [441] [442] [443] [444] [445]), FR-210575 (Fujisawa [446]), MDL-101002 (Hoechst Marion Roussel, now sanofi [447, 448]), and raxofelast (IRFI-016, Biomedica Foscama Industria [449–452]). "

    Full-text · Dataset · Apr 2013
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    • "), CPI-1189 (Centaur [433] [434]), disufenton sodium (Cerovive, NXY-059, AstraZeneca, which was in Phase III clinical trials for the treatment of acute ischemic stroke [435] [436] [437] [438] [439] [440] [441] [442] [443] [444] [445]), FR-210575 (Fujisawa [446]), MDL-101002 (Hoechst Marion Roussel, now sanofi [447, 448]), and raxofelast (IRFI-016, Biomedica Foscama Industria [449–452]). "

    Full-text · Dataset · Apr 2013
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    ABSTRACT: The concept of neuroprotective therapy for acute ischemic stroke to salvage tissue at risk and improve functional outcome is based on sound scientific principles and extensive preclinical animal studies demonstrating efficacy. The failure of most neuroprotective drugs in clinical trials has been due to inadequate preclinical testing and flawed clinical development programs. The Stroke Therapy Academic Industry Roundtable (STAIR) group has outlined rational approaches to preclinical and clinical studies. The positive results from the first Stroke-Acute-Ischaemic-NXY-Treatment (SAINT-I) trial of the free-radical spin-trap drug, NXY-059, which followed many of the STAIR guidelines, reinvigorated enthusiasm in neuroprotection, but the SAINT-II trial did not replicate the positive effect on the same primary prespecified outcome measure. This has led to concerns about the future of neuroprotection as a therapeutic strategy for acute ischemic stroke. We discuss new suggestions to bridge the chasm between preclinical animal modeling and acute human stroke trials to potentially enhance the future assessment of novel neuroprotective drugs.
    No preview · Article · May 2007 · Annals of Neurology
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