The ALIAS Pilot Trial

Abstract

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

Multifunctional Actions of Approved and Candidate Stroke Drugs

“…The ALIAS pilot trial suggested a favorable outcome when thrombolysis was combined with albumin. 100 Synergistic effects of albumin with thrombolysis were also demonstrated in a study using a rat stroke model in which the combination therapy improved microvascular hemodynamics.…”

“…The authors of that study interpreted the results as a sign for efficacy, based on comparison of higher doses with lower doses and in comparison with a historical control group. 99,100 A randomized, multicenter, double-blind, placebocontrolled trial (ALIAS Phase III Trial, www.clinicaltrials. gov; NCT00235495) is currently being conducted.…”

Hypoalbuminemia in acute ischemic stroke patients: frequency and correlates

“…Proposed beneficial effects of higher serum albumin level include binding to free fatty acids, inhibition of oxygen radical production and support of endothelial function. Recent clinical study suggests that 25% human albumin in doses ranging up to 2.05 g/kg is well tolerated by patients with acute ischemic stroke and may have beneficial effect on stroke outcome Palesch et al, 2006). Patients with low serum albumin could be a risk of severe stroke due to the insufficient neuroprotection mediated by albumins.…”

Stroke pathophysiology: management challenges and new treatment advances

“…Recent data from a phase I dose-escalation study provide evidence that human serum albumin is safe after stroke, despite a mild-to-moderate increase in pulmonary edema, even when given with thrombolytic therapy (26). The study provided preliminary evidence of efficacy, with patients in the highest dose tiers having about an 80% greater chance of good outcome at 3 months than the lower dose tiers (57). There also seemed to be a synergistic effect between albumin and thrombolytic therapy.…”