The goal of the trial is to determine whether human albumin, administered within 5 hours of symptom onset, improves the 3-month outcome of subjects with acute ischemic stroke.
Human serum albumin, at 2 g/kg, administered over 2 hours by intravenous infusion, will be compared to placebo (isovolumic normal saline) among patients with acute ischemic stroke. All patients will have a baseline stroke severity measured as NIH Stroke scale score > 5. Patients will treated according to the best standard of care including concurrent treatment with intravenous or intra-arterial thrombolysis where appropriate. The primary outcome will be determined at 3 months. The primary hypothesis is that, using the composite outcome of a modified Rankin score 0-1 or NIH stroke scale score 0-1 at 3 months (or both), the proportion of patients with improved outcomes will be greater by 10% or more in the active treatment group. [The current trial is termed "Part 2" and incorporates revisions to the initial protocol that were instituted after the DSMB suspended subject recruitment because of a safety concern after 434 subjects had been enrolled. The protocol revisions of Part 2 resulted from the study team's thorough review of the Part-1 safety data and were designed to optimize safety going forward.]
Trial Stopped: Recruitment halted by DSMB following interim analysis.
- Placebo Drug
Intervention Desc: equivalent volume of saline control ARM 1: Kind: Experimental Label: 2 Description: Treatment with same volume of normal saline
- Albumin Drug
Other Names: BUMINATE 25%, Albumin (Human) Intervention Desc: Albumin is the protein of the highest concentration in plasma. Albumin transports many small molecules in the blood (for example, bilirubin, calcium, progesterone, and drugs). It is also of prime importance keeping the fluid from the blood from leaking out into the tissues.
- Human serum albumin infusion Biological
Intervention Desc: human albumin, 25%, 2.0g/kg intravenously (or equivalent volume of saline control), infused over 2 h, commencing within 5 hours of stroke onset ARM 1: Kind: Experimental Label: 1 Description: Treatment with 25% Albumin, 2.0 g/kg ARM 2: Kind: Experimental Label: 2 Description: Treatment with same volume of normal saline
- Allocation: Randomized
- Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
- Purpose: Treatment
- Endpoint: Efficacy Study
- Intervention: Parallel Assignment
Intravenous infusion of albumin or placebo over 2 hours. Clinic visit for 3 month assessment and telephone interviews (30 min.) for clinical and quality of life assessments at 1, 6, 9 and 12 months.
|Type||Measure||Time Frame||Safety Issue|
|Primary||90-day outcome as measured by the modified Rankin Scale (mRS) and National Institutes of Health Stroke Scale (NIHSS).|
|Secondary||Mortality, mRS, NIHSS, BI, SSQOL, EuroQOL, or intracerebral hemorrhage.|
|Primary||NIHSS and mRS -- favorable outcome defined as either NIHSS 0-1 or mRS 0-1, or both||at 3 months||Yes|
|Secondary||Overall clinical outcome (as assessed by global statistical test of NIHSS, mRS, and BI scores)||at 3 months||Yes|
|Secondary||mRS (dichotomized and full-scale)||at 1, 3, 6, 9, and 12 months||Yes|
|Secondary||Symptomatic ICH||within 24 hours||Yes|
|Secondary||Congestive heart failure||within 48 hours||Yes|
|Secondary||Pulmonary edema||within 48 hours||Yes|
|Secondary||Barthel Index||at 3 and 12 months||Yes|
|Secondary||Quality-of-life measures: EuroQol at 3 and 12 months, and SSQO at 3 months||at 3 and 12 months||Yes|
|Secondary||Recurrent ischemic stroke||at 3, 6, 9, and 12 months||Yes|
|Secondary||Death within 3 months and at 12 months after randomization||within 3 months and at 12 months||Yes|
|Secondary||Cognition (Trailmaking A and B)||at 3 months||Yes|