ALIAS-Part 2
Albumin Therapy for Neuroprotection in Acute Ischemic Stroke
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Status:
Trial is ongoing as ALIAS Trial-Part 2. [The original trial, ALIAS-Part 1, was placed on hold by the DSMB in Dec. 2007 owing to a safety concern after 434 subjects had been enrolled. The DSMB recommended that revisions be instituted so as to enable the trial to resume with improved safety. Safety analyses of the data were then conducted and a revised proposal was constructed, consisting of revisions to the protocol and analysis plan, and a comprehensive site training plan. The DSMB and NINDS recommended restarting the trial as ALIAS Trial - Part 2. Data from Part 1 of ALIAS will be used in a combined meta-analysis after completion of Part 2.] Part 2 is structured as a separate trial requiring 1,100 subjects (1:1 randomization to albumin vs. placebo), powered to detect a 10% absolute effect size difference in the primary outcome. The first subject was randomized into the ALIAS Trial-Part 2 on February 27, 2009. Approximately 70 sites are currently activated. Subject recruitment is expected to take 2-3 years.
Purpose:
To determine whether human serum albumin at 2g/kg given over 2 hours, to ischemic stroke victims within 5 hours of stroke onset, results in improved outcome at 3 months.
Interventions:
Albumin
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.
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Placebo
A placebo is a substance or procedure which a patient accepts as a medicine or therapy but which has no specific therapeutic activity for the condition.
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Location(s):
United States & Canada
Year Started:
2006
Design:
Randomized, double-blinded, placebo-controlled, multicenter clinical trial.
Inclusion Criteria
Ischemic stroke with NIHSS score of 6 or greater; baseline NIHSS score is assessed at the time of tPA infusion in tPA cohort, and at randomization in the non-tPA cohort; initiation of ALB/placebo within 5 hours of stroke onset; for the tPA cohort, ALB/placebo infusion must be started within 60 minutes of the onset of the tPA bolus (90 min is permitted if awaiting baseline troponin result); ALB/placebo infusion must not delay standard-of-care thrombolytic therapy.
Exclusion Criteria
Age greater than 83 years. Elevated serum troponin level on admission > 0.1 mcg/L. 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; 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; suspicion of aortic dissection on admission; or acute arrhythmia (including any tachy- or bradycardia) with hemodynamic instability.
Findings on physical examination of any of the following: (a)jugular venous distention (JVP > 4 cm above the sternal angle); (b) 3rd heart sound; (c) resting tachycardia (heart rate > 100/min) attributable to congestive heart failure; (d) abnormal hepatojugular reflux; (e) lower extremity pitting edema attributable to congestive heart failure; and/or (f) definite chest x-ray evidence of pulmonary edema, current acute or chronic lung disease requiring supplemental chronic or intermittent oxygen therapy.
Planned acute use of 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. This standard was set in the IMS-1 study, where safety of the IV+IA tPA therapy was shown.
Other exclusions include: stroke occurring in-hospital; historical modified Rankin Scale (mRS) of 2 or greater (including pts living in a nursing home or who are not fully independent); fever, defined as core body temperature > 37.5 C (99.5 F); 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 allergy to natural rubber latex; severe chronic anema (Hgb < 7.5 g/L); 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.
Patient Involvement:
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.
Primary Outcome:
90-day outcome as measured by the modified Rankin Scale (mRS) or National Institutes of Health Stroke Scale (NIHSS).
Secondary Outcome:
Mortality, mRS, NIHSS, BI, SSQOL, EuroQOL, or intracerebral hemorrhage.
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Source of Information:
Correspondence with trial coordinator [September 2005].
Presented at the 2006 International Stroke Conference [February 2006].
Presented at the 2006 International Symposium on Neurodegeneration and Neuroprotection, Muenster, Germany.
Correspondence with principal investigator [August 2006].
Presented at the 2007 International Stroke Conference [February 2007].
Presented at the 2008 International Stroke Conference (February 2008).
Presented at the 2009 International Stroke Conference (February 2009).
Correspondence with PI 4/24/00.
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Web Links and Publications:
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This information last updated on: 4/26/2009
Reviewed on: 10/19/2009.
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