Published Online
on June 29, 2006

A more recent version of this article appeared on August 1, 2006

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Submitted on March 24, 2006
Accepted on April 13, 2006

The ALIAS Pilot Trial. A Dose-Escalation and Safety Study of Albumin Therapy for Acute Ischemic Stroke--I: Physiological Responses and Safety Results

Myron D. Ginsberg MD^*; Michael D. Hill MD, MSc; Yuko Y. Palesch PhD; Karla J. Ryckborst BA, RN; and Diego Tamariz MD

From the Department of Neurology, University of Miami Miller School of Medicine, Miami, Fla (M.D.G., D.T.); 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--In preclinical stroke models, high-dose human albumin confers robust neuroprotection. We investigated the safety and tolerability of this therapy in patients with acute ischemic stroke.

Methods--The ALIAS (Albumin in Acute Stroke) Pilot Clinical Trial used a multiple-tier, open-label, dose-escalation design. Subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received a 2-hour infusion of 25% human albumin (ALB) beginning within 16 hours of stroke onset. Six successive ALB dose tiers were assessed ranging from 0.34 to 2.05 g/kg. Neurologic and cardiac function was sequentially monitored. At 3 months, the NIHSS, modified Rankin Scale, and Barthel Index were measured.

Results--Eighty-two subjects (mean age, 65 years) received ALB at 7.8±3.4 hours after stroke onset (mean±standard deviation). Forty-two patients also received standard-of-care intravenous tissue plasminogen activator (tPA). Vital signs were unaltered by ALB treatment. Dose-related increases in plasma albumin and mild hemodilution were maximal at 4 to 12 hours. Age-related plasma brain natriuretic peptide levels increased at 24 hours after ALB but did not predict cardiac adverse events. The sole ALB-related adverse event was mild or moderate pulmonary edema in 13.4% of subjects, which was readily managed with diuretics. In the tPA-treated subgroup, symptomatic intracranial hemorrhage occurred in only one of 42 subjects.

Conclusions--Twenty-five percent human albumin in doses ranging up to 2.05 g/kg was tolerated by patients with acute ischemic stroke without major dose-limiting complications. tPA therapy did not affect the safety profile of ALB. The companion article presents neurologic outcome data and efficacy analysis in these subjects.

Key words: ischemia • neuroprotection • outcome • stroke • thrombolysis

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