title: The Albumin in Subarachnoid Hemorrhage (ALISAH) multicenter pilot clinical trial: safety and neurologic outcomes.
abstract: OBJECTIVE
  Human albumin has been shown to exert neuroprotective effects in animal models of cerebral ischemia and humans with various intracranial pathologies. We investigated the safety and tolerability of 25% human albumin in patients with subarachnoid hemorrhage.
  
  
  METHODS
  The Albumin in Subarachnoid Hemorrhage (ALISAH) Pilot Clinical Trial was an open-label, dose-escalation study. We intended to study 4 different dosages of albumin of increasing magnitude (0.625 g/kg: Tier 1; 1.25 g/kg: Tier 2; 1.875 g/kg: Tier 3; and 2.5 g/kg: Tier 4). Each dosage was to be given to 20 adult patients. Treatment was administered daily for 7 days. We investigated the maximum tolerated dose of albumin based on the rate of severe-to-life-threatening heart failure and anaphylactic reaction and functional outcome at 3 months.
  
  
  RESULTS
  We treated 47 adult subjects: 20 in Tier 1; 20 in Tier 2; and 7 in Tier 3. We found that doses ranging up to 1.25 g/kg/day×7 days were tolerated by patients without major dose-limiting complications. We also found that outcomes trended toward better responses in those subjects enrolled in Tier 2 compared with Tier 1 (OR, 3.0513; CI, 0.6586-14.1367) and with the International Intraoperative Hypothermia for Aneurysm Surgery Trial cohort (OR, 3.1462; CI, 0.9158-10.8089).
  
  
  CONCLUSIONS
  Albumin in doses ranging up to 1.25 g/kg/day×7 days was tolerated by patients with subarachnoid hemorrhage without major complications and may be neuroprotective. Based on these results, planning of the ALISAH II, a Phase III, randomized, placebo-controlled trial to test the efficacy of albumin, is underway.
  
  
  BACKGROUND
  URL: http://clinicaltrials.gov. Unique identifier: NCT00283400.
authors.affiliation: Department of Neurology, Baylor College of Medicine, 6501 Fannin Street, NB 302, Houston, TX 77030, USA. jisuarez@bcm.edu
authors.forename: Jose I
authors.initials: JI
authors.lastname: Suarez
authors.forename: Renee H
authors.initials: RH
authors.lastname: Martin
authors.forename: Eusebia
authors.initials: E
authors.lastname: Calvillo
authors.forename: Catherine
authors.initials: C
authors.lastname: Dillon
authors.forename: Eric M
authors.initials: EM
authors.lastname: Bershad
authors.forename: R Loch
authors.initials: RL
authors.lastname: Macdonald
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.forename: Robert
authors.initials: R
authors.lastname: Harbaugh
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000418:Albumins / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D003627:Data Interpretation, Statistical; D004185:Disability Evaluation; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D023261:Glasgow Outcome Scale; D006801:Humans; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000209:etiology* / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010346:Patient Care Management; D010865:Pilot Projects; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000453:epidemiology; D018401:Sample Size; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D018696:Neuroprotective Agents