Treatment of Subarachnoid Hemorrhage With Human Albumin (ALISAH)
The proposed study was set up to 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, likes 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 was to 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 was to be evaluated in the first group of 20 subjects. A specific safety threshold was defined based on data from previous studies. The Data and Safety Monitoring Board approved or disapproved advancing to the next higher HA dosage based on the evaluation of the rate of congestive heart failure (CHF). The study assessed three outcomes: safety and tolerability of the HA dosages and the functional outcome. The primary tolerability outcome was defined as the subject's ability to receive the full allocated dose of HA without incurring frank CHF that requires termination of treatment. Secondary safety outcomes were 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 was measured to obtain a preliminary estimate of the treatment effect of HA. The timeline of the study is three years.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Subarachnoid Hemorrhage With Human Albumin|
- Number of participatns with cardiovascular adverse events as a measure of safety and tolerability [ Time Frame: Up to 48 hours after treatment administration ] [ Designated as safety issue: Yes ]The study will investigate the number of patients experiencing moderate-to-severe acute heart failure for any given dosage tier directly related to treatment administration. Specifically, if at least 2 patients per dosage tier experience such serious event the study will be terminated.
- GOS [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]The study will measure the the Glasgow Outcome Scale to obtain preliminary estimates of treatment effects.
- mRs [ Time Frame: 3 months after study enrollment ] [ Designated as safety issue: No ]The study will measure the the modified Rankin Scale to obtain preliminary estimates of treatment effects.
- NIHSS [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]The study will measure the NIH Stroke Scale to obtain preliminary estimates of treatment effects.
- SIS [ Time Frame: 3 months after enrollment ] [ Designated as safety issue: No ]The study will measure the Stroke Impact Scale to obtain preliminary estimates of treatment effects.
|Study Start Date:||June 2006|
|Study Completion Date:||May 2011|
|Primary Completion Date:||July 2010 (Final data collection date for primary outcome measure)|
Experimental: 25% human albumin
Subjects will be entered into one of 4 increasing dosages of 25% human albumin sequentially. Once the first 20 subjects have been enrolled and the DSMB reviews data and approves moving to the next dosage tier patients will be entered into the following dosage tier.
Drug: Human Albumin
25% human albumin given in four escalating doses:
Other Name: Albumin