Albumin in Acute Ischemic Stroke Trial

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. \[The current trial is termed "Part 2" and incorporates revisions to the initial protocol that were instituted after the Data Safety Monitoring Board (DSMB) suspended subject recruitment because of a safety concern after 434 subjects had been enrolled. The protocol revisions of Part 2 resulted from the study team's thorough review of the Part-1 safety data and were designed to optimize safety going forward.\]

Eligibility Criteria:
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 Tissue Plasminogen Activator (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 Modified Rankin Score (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 \> 37.5° C (99.5°F).
* 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.