ALIAS (Albumin in Acute Ischemic Stroke) Trials

Abstract

BACKGROUND AND PURPOSE The Albumin in Acute Stroke (ALIAS) Part 1 and 2 Trials evaluated whether 25% human serum albumin improves clinical outcomes after acute ischemic stroke above and beyond standard of care using similar protocols. The Part 1 Trial ended prematurely due to safety concerns, and the Part 2 Trial terminated early due to futility of finding a statistically significant effect of ALB over saline (control) administration. We combine the subject-level data of the Part 1 and 2 Trials to re-evaluate the efficacy and safety outcomes with the larger sample size. METHODS The combined data analyses closely follow those conducted in the Part 2 Trial. The primary outcome is the composite of the modified Rankin Scale and the NIH Stroke Scale defined as a composite of mRS 0-1 and/or NIHSS 0-1 at 90 days from randomization. The unadjusted analyses use a simple Chi-square test and those adjusting for baseline covariates use a generalized linear model with log link (to obtain relative risks). RESULTS The participant characteristics at baseline were generally similar between the treatment groups and between Trials; however, thrombolysis use was greater in Part 2 (84% vs 75%), and the upper age limit imposed in Part 2 resulted in a younger sample (mean age in Part 1 was 69 vs 64 in Part 2). In the combined sample the proportions of good outcome in the two treatment groups were identical (41%). Similar results were observed in all secondary efficacy outcomes. Pulmonary edema was a consistent safety concern, with a six-fold increase in the ALB arm (13%) compared to Saline (2%) (RR=7.76, 95% CI 3.87-15.57). CONCLUSIONS Treatment with intravenous albumin 25% at 2 g/kg was not associated with improved outcome at 90 days and was associated with increased rates of intracerebral hemorrhage and pulmonary edema.

TGFβ signaling is associated with changes in inflammatory gene expression and perineuronal net degradation around inhibitory neurons following various neurological insults

“…According to a recent report 62 , however, albumin administration has no therapeutic benefits and is in fact associated with greater adverse events such as increased rates of intracerebral hemorrhage or pulmonary edema. Although such discrepancy between preclinical evidence and the clinical trial remains unexplained yet 62 , the effect of albumin exposure shown in the present study might contribute in part to its adverse effect. We used albumin at a concentration up to the one corresponding to 100% of serum concentration (0.4 mM) with an assumption of maximum disruption of BBB.…”

Critical appraisal of the role of serum albumin in cardiovascular disease

“…Despite the apparent relations between higher SA concentration and better outcome from epidemiologic evidence, active therapy with albumin solution in acute ischemic stroke did not improve the outcome. This was true also for intracerebral hemorrhage and pulmonary edema where increased risk rates were identified [ 54 , 55 ].…”

Improving Cerebral Blood Flow after Arterial Recanalization: A Novel Therapeutic Strategy in Stroke

“…As a hemodiluting agent, albumin has been shown to increase collateral formation and enhance reperfusion after distal MCA occlusion in mice [ 72 ]. However, the clinical trial ALIAS (Albumin in Acute Ischemic) showed that treatment with intravenous albumin in stroke patients was not associated with improved outcome at 90 days, and was associated with increased rates of HT and pulmonary edema [ 73 ]. Collateral flow improvement by chemokines and growth factors, including vascular endothelial growth factor (VEGF) and statins, has also been evaluated in ischemic stroke.…”