The Albumin in Subarachnoid Hemorrhage (ALISAH) multicenter pilot clinical trial: safety and neurologic outcomes.

Abstract

BACKGROUND AND PURPOSE:

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.

CLINICAL TRIAL REGISTRATION:

URL: http://clinicaltrials.gov. Unique identifier: NCT00283400.

• Authors: Jose I Suarez, Renee H Martin, Eusebia Calvillo, Catherine Dillon, Eric M Bershad, R Loch Macdonald, John Wong, Robert Harbaugh, ALISAH Investigators
• Journal: Stroke (Stroke) Vol. 43 Issue 3 Pg. 683-90 (Mar 2012) ISSN: 1524-4628 [Electronic] United States
• PMID: 22267829 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Albumins
• Neuroprotective Agents

Topics

• Acute Disease
• Adult
• Aged
• Albumins (adverse effects, therapeutic use)
• Blood Pressure (physiology)
• Cardiovascular Diseases (chemically induced, epidemiology)
• Data Interpretation, Statistical
• Disability Evaluation
• Dose-Response Relationship, Drug
• Female
• Follow-Up Studies
• Glasgow Outcome Scale
• Humans
• Male
• Middle Aged
• Nervous System Diseases (etiology, prevention & control)
• Neuroprotective Agents (adverse effects, therapeutic use)
• Patient Care Management
• Pilot Projects
• Respiratory Tract Diseases (chemically induced, epidemiology)
• Sample Size
• Subarachnoid Hemorrhage (complications, drug therapy, psychology)
• Treatment Outcome