The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--II: neurologic outcome and efficacy analysis.
OBJECTIVE
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.
Palesch
Yuko Y
YY
Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, Florida 33101, USA.
Hill
Michael D
MD
Ryckborst
Karla J
KJ
Tamariz
Diego
D
Ginsberg
Myron D
MD
D000368:Aged; D000418:Albumins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D002545:Brain Ischemia / Q000150:complications*; D002543:Cerebral Hemorrhage / Q000139:chemically induced; D004232:Diuretics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009420:Nervous System / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D010865:Pilot Projects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy; D012709:Serum Albumin / Q000378:metabolism; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
D000418:Albumins; D004232:Diuretics; D005343:Fibrinolytic Agents; D018696:Neuroprotective Agents; D012709:Serum Albumin; D010959:Tissue Plasminogen Activator