on June 29, 2006
Published online before print June 29, 2006, doi: 10.1161/01.STR.0000231389.34701.b5
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Submitted on March 24, 2006
From the Department of Neurology, University of Miami Miller School of Medicine, Miami, Fla (D.T., M.D.G.); The Departments of Clinical Neurosciences and Community Health Sciences, University of Calgary, Alberta, Canada (M.D.H., K.J.R.); and the Department of Biostatistics, Bioinformatics and Epidemiology, Medical University of South Carolina, Charleston, SC (Y.Y.P.). * To whom correspondence should be addressed. E-mail: mdginsberg{at}stroke.med.miami.edu.
Background and Purpose--High-dose human albumin (ALB) is robustly neuroprotective in rodent stroke models. A phase I dose-escalation study was conducted to assess the safety of ALB therapy in ischemic stroke. We analyzed the data for preliminary evidence of treatment efficacy. Methods--Eighty-two subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received 25% ALB beginning within 16 hours of stroke onset. Six successive ALB dose tiers were assessed (range, 0.34 to 2.05 g/kg). Forty-two patients also received standard-of-care intravenous tissue plasminogen activator (tPA). Efficacy outcomes were determined at 3 months. We compared the highest three, putatively therapeutic ALB dose tiers (1.37 to 2.05 g/kg) with the lowest three, presumed subtherapeutic doses (0.34 to 1.03 g/kg) and with historical cohort data derived from the NINDS rt-PA Stroke Study. Results--After adjusting for the tPA effect, the probability of good outcome (defined as modified Rankin Scale 0 to 1 or NIH Stroke Scale 0 to 1 at 3 months) at the highest three ALB doses was 81% greater than in the lower dose-tiers (relative risk [RR], 1.81; 95% confidence interval [CI], 1.11 to 2.94) and was 95% greater than in the comparable NINDS rt-PA Stroke Study cohort (RR, 1.95; 95% CI, 1.47 to 2.57). The tPA-treated subjects who received higher-dose ALB were three times more likely to achieve a good outcome than subjects receiving lower-dose ALB, suggesting a positive synergistic effect between ALB and tPA. Conclusions--Our data suggest that high-dose ALB therapy may be neuroprotective after ischemic stroke. These results have led to a multicenter, randomized, placebo-controlled efficacy trial of ALB in acute ischemic stroke--the ALIAS Phase III Trial.
Accepted on April 13, 2006
The ALIAS Pilot Trial. A Dose-Escalation and Safety Study of Albumin Therapy for Acute Ischemic Stroke--II: Neurologic Outcome and Efficacy Analysis
Yuko Y. Palesch PhD;
Key words: ischemia • neuroprotection • stroke • thrombolysis • outcome
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