ALIAS Phase IIi Multicenter Clincal Trial -- Albumin in Acute Ischemic Stroke

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DESCRIPTION (provided by applicant): The objective of this competitive renewal application is to bring to completion the ALIAS (Albumin in Acute Stroke) Multicenter Clinical Trial, whose aim is to ascertain whether high-dose human albumin therapy (ALB) confers neuroprotection in subjects with acute ischemic stroke. This NINDS-funded trial, in progress at around 60 U.S. and Canadian clinical sites, follows upon extensive preclinical studies showing that ALB therapy is highly neuroprotective; and a dose-escalation Pilot Trial, in which the safety and tolerability of this therapy in stroke patients were demonstrated and a preliminary signal of efficacy was obtained. Based on DSMB-identified safety concerns arising in the first 434 subjects of the ALIAS Multicenter Trial, detailed unblinded safety analyses were conducted and factors were identified that were incorporated into a revised protocol (including upper age limit, mandatory fluid restriction, mandatary diuretic therapy) to improve safety. The ALIAS Part 2 Trial then re-commenced in Feb. 2009 and has since enrolled over 280 subjects of the 1,100 required. The ALIAS Part 2 Trial Is a randomized, double-blinded, placebo-controlled Phase III multicenter clinical trial in patients with acute ischemic stroke whose baseline NIHSS score is >6 and who can be treated with study drug within 5 hours of stroke onset. Standard-of-care thrombolytic therapy (IV and/or IA tPA and mechanical clot lysis) Is permitted. The primary aim of the trial is to ascertain whether ALB therapy confers neuroprotection over and above the best standard of care: specifically, to determine whether ALB therapy increases the proportion of subjects with favorable outcome compared to placebo therapy. Favorable outcome is defined as either an NIHSS score of 0 or 1, or a modified Rankin Score (mRS) of 0 or 1, or both, measured at 3 months from randomization. Subjects are followed out to 12 months. A total of 1,100 subjects will be enrolled. Selected European sites may be added. The ALIAS Trial affords the unique opportunity to apply a preclinically highly effective strategy to treat ischemic stroke using a dose and timing that closely replicate the preclinical setting in which efficacy was shown. PUBLIC HEALTH RELEVANCE: Stroke is the third leading cause of death and the major cause of chronic disability. There are currently no clinically proven agents to protect the brain from irreversible Injury in stroke. Lab studies have shown that high-dose albumin therapy is strongly protective in stroke models. The ALIAS Multicenter Trial is a randomized, placebo-controlled study to assess whether this therapy improves neurological and functional outcome in ischemic stroke patients. If it does so, it will become a standard of care throughout the world.