albumin in acute ischemic stroke trial

Conditions: Ischemic Stroke

Summary: 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.

Keywords: stroke