Albumin in Acute Ischemic Stroke Trial
- Conditions
- Ischemic Stroke
- Interventions
- Drug: SalineBiological: Albumin
- Registration Number
- NCT00235495
- Lead Sponsor
- University of Miami
- Brief 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.
- Detailed Description
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. \[The current trial is termed "Part 2" and incorporates revisions to the initial protocol that were instituted after the Data Safety Monitoring Board (DSMB) suspended subject recruitment because of a safety concern after 434 subjects had been enrolled. The protocol revisions of Part 2 resulted from the study team's thorough review of the Part-1 safety data and were designed to optimize safety going forward.\]
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 841
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Saline Saline Saline (isotonic solution), 8 ml/kg, infused intravenously over a 2-hour period Albumin (ALB) Albumin Albumin (human albumin, 25% solution, 2.0 g/kg), infused intravenously over a period of 2 hours
- Primary Outcome Measures
Name Time Method The Number of Participants With Favorable Outcome Defined as National Institute of Health Stroke Scale (NIHSS) Score of 0-1 and/or Modified Rankin Scale (mRS) of 0-1. at 3 months The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit. The mRS ranges from 0-6 representing perfect health without symptoms to death. A score of 0 is no symptoms at all and a score of 1 is no significant disability. Able to carry out all usual duties and activities.
- Secondary Outcome Measures
Name Time Method Number of Participants With a Composite Outcome of mRS 0-1 and/or NIHSS 0-1 and/or Decrease in NIHSS From Baseline by 10 or More Points at 3 months Number of Participants With a NIHSS of 0-1 at 24 Hours at 24 hours The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit.
Number of Participants With a NIHSS 0-1 at 90 Days. at 90 days The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool that provides a quantitative measure of stroke-related neurologic deficit. The scores range from 0 to 42 with a score of greater than 20 indicating severe neurologic deficit.
The Number of Participants With a Score on the mRS 0-1 at 90 Days. at 90 days The mRS ranges from 0-6 representing perfect health without symptoms to death. 0 = No symptoms at all. 1 = No significant disability. Able to carry out all usual duties and activities. 2 = Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 = Moderate disability. Requires some help, but able to walk unassisted. 4 = Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 = Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 = Dead.
The Number of Participants With a Score on the mRS of 0-2 at 90 Days. at 90 days The mRS ranges from 0-6 representing perfect health without symptoms to death. 0 = No symptoms at all. 1 = No significant disability. Able to carry out all usual duties and activities. 2 = Slight disability. Unable to carry out all previous activities but able to look after own affairs without assistance. 3 = Moderate disability. Requires some help, but able to walk unassisted. 4 = Moderately severe disability. Unable to walk unassisted and unable to attend to own bodily needs without assistance. 5 = Severe disability. Bedridden, incontinent, and requires constant nursing care and attention. 6 = Dead.
Number of Participants With a Favorable Outcome Per Modified Rankin Scare (mRS) 90 days Assessed as the final global disability level on the modified Rankin scale (mRS) at 90 days better than expectation (sliding dichotomy analysis) ) assessed in the intention to treat population.
mRS Scale:
0 - No symptoms.
1. - No significant disability. Able to carry out all usual activities, despite some symptoms.
2. - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
3. - Moderate disability. Requires some help, but able to walk unassisted.
4. - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
5. - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
6. - Dead.Barthel Index (BI) 95-100 at 90 days The Barthel Index (BI) is an ordinal scale used to measure a subject's performance in activities of daily living (ADL) in ten variables - feeding, transfer (bed to chair), grooming, toilet use, bathing, mobility on a level surface, stair use, dressing, bowels and bladder. It is an assessment of independence in ADL and is scored in increments of 5 points. the highest total score for fully independent subjects equals 100. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence.
Number of Participants With an EuroQol (EQ-5D) Favorable Score < 0.78 at 90 days The EQ-5D measures the subject's overall health state in a descriptive system of health-related quality of life (QoL) states consisting of five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) each of which can take one of three responses. The responses record three levels of severity ('no problems', 'some problems', and 'extreme problems) within a particular EQ-5D dimension. The EQ-5D results can be converted to health utility scores.
Number of Participants With a Stroke Specific Quality of Life Scale (SSQOL) Score of >=3 at 90 days Stroke, specific, health-related quality of life (SSQoL) is a self-reported survey that includes 12 domains and 49 items which are scored on a 5pt Likert response format with a lower score indicating worse function/lower ability on that item or domain. Domain scores were calculated as an unweighted average of item scores in that domain. Overall Total Score was calculated as an unweighted average of domain scores. Each Domain Score and the Overall Total Score all range from 1-5 with 1 being worst and 5 being the best. We have presented data here for the number of participants that have an unweighted average of domain scores of 3 or greater.
Trailmaking A at 90 days The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete ach part. Normally, the entire test (A and B) can be completed in 5-10 minutes.
Trailmaking B at 90 days The Trail Making Test is a neuropsychological test of visual attention and task switching that is thought to be sensitive to the presence of cerebral dysfunction. It is a timed test consisting of two parts where the subject is asked to draw a "trail" made by connecting numbers in sequential order (part A) and then in part B the combination of numbers and letters. Scoring is calculated separately for Parts A and B but both scores are provided as the minutes and seconds it takes for the subject to complete ach part. Normally, the entire test (A and B) can be completed in 5-10 minutes.
Number of Participants With Neurological Deterioration Within 48 Hours within 48 hours This is assessed as the number of participants with a neurological adverse event.
Neurological Death Within 7 Days within 7 days Recurrent Ischemic Stroke Within 30 Days within 30 days Atrial Fibrillation Within 48 Hours within 48 hours Pulmonary Edema Within 48 Hours within 48 hours Shortness of Breath Within 48 Hours within 48 hours Symptomatic Intracerebral Hemorrhage (ICH) Within 24 Hours within 24 hours Asymptomatic ICH Within 24 Hours within 24 hours Death Within 30 Days within 30 days Death Within 90 Days within 90 days
Trial Locations
- Locations (89)
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Memorial Hermann Texas Medical Center
🇺🇸Houston, Texas, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
St. Elizabeth Medical Center South
🇺🇸Edgewood, Kentucky, United States
University of North Carolina at Chapel Hill
🇺🇸Chapel Hill, North Carolina, United States
Wake Med Health and Hospitals
🇺🇸Raleigh, North Carolina, United States
University of Pennsylvania Medical Center
🇺🇸Philadelphia, Pennsylvania, United States
Mercy Health Fairfield Hospital
🇺🇸Fairfield, Ohio, United States
Virginia Commonwealth University Medical Center
🇺🇸Richmond, Virginia, United States
Fairview Southdale Hospital
🇺🇸Edina, Minnesota, United States
Rambam Health Care Campus
🇮🇱Haifa, Israel
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
Intercoastal Neurology/Medical Research Center
🇺🇸Sarasota, Florida, United States
Jackson Memorial Hospital, University of Miami
🇺🇸Miami, Florida, United States
University of Florida/Shands
🇺🇸Jacksonville, Florida, United States
Hopital Charles LeMoyne, Centre de Recherche
🇨🇦Greenfield Park, Quebec, Canada
Helsinki University Central Hospital
🇫🇮Helsinki, Finland
The Villages Research Group
🇺🇸Ocala, Florida, United States
Hadassah Medical Organization, Hadassah University Hospital
🇮🇱Ein Kerem, Jerusalem, Israel
Christiana Hospital
🇺🇸Newark, Delaware, United States
Upper Chesapeake Medical Center
🇺🇸Bel Air, Maryland, United States
University of Arizona Medical Center
🇺🇸Tucson, Arizona, United States
Neuroscience Research Institute at Florida Hospital Orlando
🇺🇸Orlando, Florida, United States
Centre de Sante et de Service Sociaux de Chicoutimi
🇨🇦Saguenay, Quebec, Canada
Soroka Medical Center
🇮🇱Beer Sheva, Israel
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Hahnemann University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Seton Medical Center
🇺🇸Austin, Texas, United States
Foothills Hospital, University of Calgary
🇨🇦Calgary, Alberta, Canada
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Trillium Health Centre
🇨🇦Mississauga, Ontario, Canada
Grey Nuns Community Hospital
🇨🇦Edmonton, Alberta, Canada
Queen Elizabeth II Health Science Centre
🇨🇦Halifax, Nova Scotia, Canada
Vancouver General Hospital
🇨🇦Vancouver, British Columbia, Canada
Tampere University Hospital
🇫🇮Tampere, Finland
London Health Sciences Centre-University Hospital
🇨🇦London, Ontario, Canada
University of Toronto, St. Michael's Hospital
🇨🇦Toronto, Ontario, Canada
Thunder Bay Regional Health Sciences Centre
🇨🇦Thunder Bay, Ontario, Canada
Chaim Sheba Medical Center at Tel-Hashomer
🇮🇱Tel Hashomer, Ramat Gan, Israel
El Camino Hospital
🇺🇸Mountain View, California, United States
University of Arizona Medical Center-South Campus
🇺🇸Tucson, Arizona, United States
John Muir Medical Ctr-Concord
🇺🇸Concord, California, United States
John Muir Medical Ctr-Walnut Creek
🇺🇸Walnut Creek, California, United States
Grady Memorial Hospital
🇺🇸Atlanta, Georgia, United States
UCLA Medical Center, Santa Monica
🇺🇸Santa Monica, California, United States
O'Connor Hospital
🇺🇸San Jose, California, United States
Atlantic Neuroscience Institute, Overlook Hospital
🇺🇸Summit, New Jersey, United States
Emory University Hospital
🇺🇸Atlanta, Georgia, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
St. Elizabeth Hospital
🇺🇸Florence, Kentucky, United States
New York Methodist Hospital
🇺🇸Brooklyn, New York, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Sacred Heart Medical Center
🇺🇸Springfield, Oregon, United States
HealthEast Care System/St. Joseph's Hospital
🇺🇸Saint Paul, Minnesota, United States
Abington Memorial Hospital
🇺🇸Abington, Pennsylvania, United States
MetroHealth Medical Center
🇺🇸Cleveland, Ohio, United States
Buffalo General Medical Center
🇺🇸Buffalo, New York, United States
Mercy Hospital of Buffalo
🇺🇸Buffalo, New York, United States
Winthrop University Hospital
🇺🇸Mineola, New York, United States
Penn State Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
Temple University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
Royal Island Hospital
🇨🇦Kamloops, British Columbia, Canada
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
Detroit Receiving Hospital
🇺🇸Detroit, Michigan, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
UCSF Medical Center
🇺🇸San Francisco, California, United States
UCSF-San Francisco General Hospital
🇺🇸San Francisco, California, United States
Good Samaritan Hospital
🇺🇸Cincinnati, Ohio, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
California Pacific Medical Center, Davies Campus
🇺🇸San Francisco, California, United States
California Pacific Medical Center, Pacific Campus
🇺🇸San Francisco, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Providence St. Vincent Medical Center
🇺🇸Portland, Oregon, United States
OHSU Legacy Emmanuel Hospital
🇺🇸Portland, Oregon, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States
Sinai-Grace Hospital
🇺🇸Detroit, Michigan, United States
Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota Medical Center Fairview
🇺🇸Minneapolis, Minnesota, United States
University of Cincinnati Medical Center
🇺🇸Cincinnati, Ohio, United States
Bethesda North Hospital
🇺🇸Cincinnati, Ohio, United States
Froedtert Memorial Hospital
🇺🇸Milwaukee, Wisconsin, United States
Loyola University Medical Center
🇺🇸Maywood, Illinois, United States
University of Kentucky Hospital
🇺🇸Lexington, Kentucky, United States
Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
The Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada