ALIAS - Pilot
Albumin in Acute Stroke
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Status:
Trial complete. Results presented in February 2005 and published August 2006.
Purpose:
To determine the safety and efficacy of administering moderate-dose human serum albumin intravenously to ischemic stroke patients.
Location(s):
Florida & Canada.
Year Started:
2003
Year Finished:
2004
Year Presented:
2005
Design:
Multi-center, non-randomized, multiple-tier, dose-escalation, pilot study with 2 cohorts and 6 tiers.
Inclusion Criteria
Patients with a history of a focal neurologic syndrome of acute onset and at least a moderate initial neurologic deficit, defined as an NIHSS score of 6 or greater; computed tomography (CT) or magnetic resonance scan excluding hemorrhage; ability to commence the intravenous infusion of 25% ALB within 16 hours after the onset of stroke symptoms (defined as the time at which the onset of a neurologic abnormality was observed or, with symptoms first noticed on awakening from sleep, the last time the patient was observed to be without stroke symptoms).
Exclusion Criteria
History and/or physical findings on admission of congestive heart failure (CHF), including jugular venous distention, third heart sound, resting tachycardia >100/min attributable to heart failure, hepatomegaly, and/or lower extremity edema attributable to heart failure or without apparent cause. (Initially, the historical CHF exclusion pertained to the preceding 6 months; this was later changed to “at any time in the past.”)
Hospitalization for acute myocardial infarction within the preceding 3 months.
Symptoms or electrocardiographic (ECG) signs of acute myocardial infarction on admission.
ECG findings and/or history or physical findings of second- or third-degree heart block or of cardiac arrhythmia associated with hemodynamic instability (in the
investigator’s judgment).
[In year 1:] admission two-dimensional echocardiographic findings of: (1) ejection fraction less than 40%; (2) moderate or severe valvular stenosis or severe
valvular insufficiency; (3) right ventricular systolic pressure 50 mm Hg; or (4) diastolic dysfunction. [In year 2, these exclusions were dropped; instead, an
echocardiogram was merely obtained within the first 24 hours.]
Acute or chronic renal failure (serum creatinine >2.0 mg/dL)
Severe anemia (hematocrit <32%)
Clinically suspected aortic dissection
Presenting symptoms and/or CT scan evidence of subarachnoid hemorrhage
Parenchymal intracerebral hemorrhage on pretreatment CT scan
Pregnancy in women aged 18 to 55 (pregnancy test required in women of childbearing age unless known to be surgically sterilized or postmenopausal)
History of allergic reaction to ALB administration
Blood pressure higher than 185/110 mm Hg at the time of ALB administration
Other active, potentially life-threatening disorders
Subjects receiving intravenous tPA were required as well to satisfy the tPA exclusion criteria used in the NINDS tPA trial19
Additional exclusion criteria introduced in January 2004 (applicable to the last 30 subjects)
Known valvular heart disease requiring medical therapy
Prosthetic heart valves
Any current chronic lung disease, including chronic obstructive pulmonary disease, bronchiectasis, past lung resection, and other lung disease that interferes
with daily activities.
Patient Involvement:
Patients are infused with a 25% solution of Human albumin over a 2 hour period beginning within 16 hours of stroke onset, and were split into two cohorts: those who received standard-of-care intravenous (IV) tissue plasminogen activator (tPA); and (2) those who did not receive tPA. NIH Stroke Scale is assessed sequentially until discharge. NIHSS, modified Rankin Scores, and Barthel Index are assessed at 1 and 3 months.
Primary Outcome:
NIHSS, modified Rankin Scores, and Barthel Index are assessed at 1 and 3 months.
Results:
Patients were split into two cohorts: those who received tpa (n=35) and those who did not (n=35). No significant differences were observed among the groups, however a dose-related trend toward clinical improvement was observed in patients within the tpa cohort, suggesting that high-dose ALB therapy may be neuroprotective after ischemic stroke. The probability of good outcome (defined as modified Rankin Scale 0 to 1 or NIH Stroke Scale 0 to 1 at 3 months) at the highest three ALB doses was 81% greater than in the lower dose-tiers (relative risk [RR], 1.81; 95% confidence interval [CI], 1.11 to 2.94) and was 95% greater than in the comparable NINDS rt-PA Stroke Study cohort (RR, 1.95; 95% CI, 1.47 to 2.57). The tPA-treated subjects who received higher-dose ALB were three times more likely to achieve a good outcome than subjects receiving lower-dose ALB, suggesting a positive synergistic effect between ALB and tPA. A larger, Phase II trial is being conducted.
Source of Information:
Presented at the 2004 International Stroke Conference [February 2004].
Presented at the 2005 International Stroke Conference [February 2005].
Stroke. 2006;37:2100-2106.
Stroke. 2006;37:2107-2114.
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This information last updated on: 8/9/2006
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