The ALIAS Pilot Trial: a dose-escalation and safety study of albumin therapy for acute ischemic stroke--I: Physiological responses and safety results.
OBJECTIVE
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.
Ginsberg
Myron D
MD
Department of Neurology (D4-5), University of Miami Miller School of Medicine, PO Box 016960, Miami, Florida 33101, USA. mdginsberg@stroke.med.miami.edu
Hill
Michael D
MD
Palesch
Yuko Y
YY
Ryckborst
Karla J
KJ
Tamariz
Diego
D
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; D020097:Natriuretic Peptide, Brain / Q000097:blood; 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*; 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; D020097:Natriuretic Peptide, Brain; D010959:Tissue Plasminogen Activator