The proposed study will evaluate the tolerability and safety of 25% human albumin (HA) therapy in patients with subarachnoid hemorrhage (SAH). It is estimated that 37,500 people in the USA have SAH every year. SAH is associated with a 51% mortality rate and one third of survivors are left functionally dependent. Cerebral vasospasm (CV) has been identified as the most important reason for neurological deterioration. CV may be due to multiple molecular mechanisms. The use of a neuroprotective agent with various actions, like HA, would be important for prevention of CV and improved clinical outcome in patients with SAH. The proposed open-label, dose-escalation study will have important public health implications by providing necessary information for a definitive phase III clinical trial regarding the efficacy of treatment with HA in patients with SAH. The study will enroll a maximum of 80 patients with SAH who meet the eligibility criteria. Four dosages of HA (0.625, 1.25, 1.875, and 2.5 g/kg) administered daily for seven days will be evaluated. The lowest dosage will be evaluated in the first group of 20 subjects. A specific safety threshold has been defined based on data from previous studies. The Data and Safety Monitoring Board will approve or disapprove advancing to the next higher HA dosage based on the evaluation of the rate of congestive heart failure (CHF). The study will assess three outcomes: safety and tolerability of the HA dosages and the functional outcome. The primary tolerability outcome will be defined as the subject's ability to receive the full allocated dose of HA without incurring frank CHF that requires termination of treatment. Secondary outcomes will be serious adverse events (including neurological and medical complications, and anaphylactic reactions). Neurological complications comprise incidence of CV, rebleeding, hydrocephalus, and seizures after treatment. The three-month functional outcome determined',by Glasgow Outcome Scale, Barthel Index, modified Rankin Scale, NIH Stroke Scale and Stroke Impact Scale will be; measured to obtain a preliminary estimate of the treatment effect of HA. The timeline of the study is three years. ? ?
|Suarez, Jose I; Martin, R H; Calvillo, E et al. (2015) Effect of human albumin on TCD vasospasm, DCI, and cerebral infarction in subarachnoid hemorrhage: the ALISAH study. Acta Neurochir Suppl 120:287-90|
|Suarez, Jose I; Martin, Renee H; Calvillo, Eusebia et al. (2012) The Albumin in Subarachnoid Hemorrhage (ALISAH) multicenter pilot clinical trial: safety and neurologic outcomes. Stroke 43:683-90|
|Goldstein, Larry B; Suarez, Jose I (2009) The quest for the ""Holy Grail"" of ischemic stroke cytoprotection: Statins may not be the answer. Neurology 73:2058-9|