Trend Toward Better Responses in Subarachnoid Hemorrhage Patients Treated with 25% Human Albumin: Pilot Study

Human albumin is known to exert a neuroprotective effect in animal models of cerebral ischemia and humans with various intracranial pathologies. Encouraged by those findings, researchers at five U.S. and Canadian centers investigated the safety and tolerability of 25% human albumin in patients with subarachnoid hemorrhage (SAH),with the goal of providing necessary information for a future definitive efficacy trial in SAH. The “Albumin in Subarachnoid Hemorrhage” (ALISAH) Pilot Clinical open-label, dose-escalation study evaluated four daily dosage tiers: 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). The maximum tolerated dose of albumin was based on the rate of severe heart failure and anaphylactic reaction, as well as functional outcome at three months. Treatment was administered daily for seven days.

A total of 47 adult subjects were enrolled: 20 in tier 1, 20 in tier 2 and seven in tier 3. No patients were enrolled in tier 4. Doses ranging up to 1.25 g/kg/day were tolerated by patients without major dose-limiting complications. Clinical outcomes trended toward better responses in subjects enrolled in tier 2 (1.25 g/kg) compared with tier 1 (odds ratio [OR], 3.0513; 95% confidence interval [CI], 0.6586-14,1367), and compared with the International Intraoperative Hypothermia for Aneurysm Surgery Trial cohort (OR, 3.1462; CI, 0.9158-10.8089).

The investigators concluded that albumin in doses ranging up to 1.25 g/kg/day for seven days was tolerated by patients with SAH without major complications and may be neuroprotective. Based on these results, planning of a Phase III, randomized, placebo-controlled trial(ALISAH II)to test the efficacy of albumin is under way, with sponsorship from the National Institute of Neurological Disorders and Stroke.