Albumin in Acute Ischemic Stroke Trial

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.]

Inclusion Criteria:

- Acute ischemic stroke

- NIH stroke scale score > 5

- Age >= 18 and <= 83

- ALB or placebo can be administered within 5 hours of symptom onset

- ALB or placebo can be administered within 60 minutes of tPA administration in the
thrombolysis group

- Signed informed consent

Exclusion Criteria:

- Episode/exacerbation of congestive heart failure (CHF) from any cause in the last 6
months. An episode of congestive heart failure is any heart failure that required a
change in medication, diet or hospitalization.

- Known valvular heart disease with CHF in the last 6 months.

- Severe aortic stenosis or mitral stenosis.

- Cardiac surgery involving thoracotomy (e.g., coronary artery bypass graft (CABG),
valve replacement surgery) in the last 6 months.

- Acute myocardial infarction in the last 6 months.

- Signs or symptoms of acute myocardial infarction, including ECG findings, on
admission.

- Baseline elevated serum troponin level on admission (>0.1 mcg/L)

- Suspicion of aortic dissection on admission.

- Acute arrhythmia (including any tachycardia - or bradycardia) with hemodynamic
instability.

- Findings on physical examination of any of the following: (1) jugular venous
distention (JVP > 4 cm above the sternal angle); (2) 3rd heart sound; (3) resting
tachycardia (heart rate > 100/min) attributable to congestive heart failure; (4)
abnormal hepatojugular reflux; (5) lower extremity pitting edema attributable to
congestive heart failure; and/or (6) definite chest x-ray evidence of pulmonary edema.

- Current acute or chronic lung disease requiring supplemental chronic or intermittent
oxygen therapy.

- Historical mRS ≥2. Patients who live in a nursing home or who are not fully
independent for activities of daily living immediately prior to the stroke are not
eligible for the trial.

- In-patient stroke. I.e., patients with a stroke occurring as a complication of
hospitalization for another condition, or as a complication of a procedure.

- Planned acute use of intra-arterial (IA) tPA or acute endovascular intervention (e.g.,
stenting, angioplasty, thrombus retrieval device use) must conform to the following
criteria: (1) begin within 5 hours of symptom onset, and (2) finish within 7 hours of
symptom-onset.

- Fever, defined as core body temperature > 37.5oC (99.5oF).

- Serum creatinine > 2.0 mg/dL or 180 µmol/L.

- Profound dehydration.

- Evidence of intracranial hemorrhage (intracerebral hematoma (ICH), subarachnoid
hemorrhage (SAH), epidural hemorrhage, acute or chronic subdural hematoma (SDH)) on
the baseline CT or MRI scan.

- History of allergy to albumin.

- History of latex rubber allergy.

- Severe chronic anemia with Hgb < 7.5 g/dL

- Pregnancy, breastfeeding or positive pregnancy test. (Women of childbearing age must
have a negative pregnancy test prior to ALB administration.)

- Concurrent participation in any other therapeutic clinical trial.

- Evidence of any other major life-threatening or serious medical condition that would
prevent completion of 3-month follow-up, impair the assessment of outcome, or in which
ALB therapy would be contraindicated or might cause harm to the subject.