Activated Protein C in Acute Stroke Trial (APCAST)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Activated Protein C in Acute Stroke Trial|
- Number of Participants With Intracranial Hemorrhage [ Time Frame: Measured within 36-48 hours of treatment ] [ Designated as safety issue: Yes ]
Intracranial Hemorrhage (ICH):
Fatal ICH: Death ascribed to ICH confirmed by autopsy or CT imaging. Major non-fatal ICH: Hemorrhage within brain parenchyma associated with neurological deterioration or evidence of subdural, epidural or intraventricular hemorrhage on CT imaging, with or without symptoms.
Symptomatic ICH: Hemorrhage within the territory of qualifying infarction with neurological deterioration as measured by > 2 point increase in the National Institutes of Health Stroke Scale (NIHSS) from previous examination; hemorrhage in different vascular territory associated with new neurologic deficit. All symptomatic ICH will be defined as a major ICH.
Asymptomatic ICH: Presence of hemorrhage within the territory of qualifying infarction without neurological deterioration ascribed to the hemorrhage or presence of hemorrhage within brain parenchyma outside the territory of qualifying infarction without new neurologic deficit (would not be considered a major ICH)
- Mean Modified Rankin Scale Score [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Measure of disability as determined by categorical assignment on modified Rankin Scale.. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.
The scale runs from 0-6, running from perfect health without symptoms to death.
0 - No symptoms.
- - No significant disability. Able to carry out all usual activities, despite some symptoms.
- - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
- - Moderate disability. Requires some help, but able to walk unassisted.
- - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
- - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
- - Dead.
- Mean Barthel Index Score [ Time Frame: 90 days ] [ Designated as safety issue: No ]
Measure of functional recovery using Barthel Index (range 0-100). The Barthel scale or Barthel ADL index is an ordinal scale used to measure performance in activities of daily living (ADL). Each performance item is rated on this scale with a given number of points assigned to each level or ranking. It uses ten variables describing ADL and mobility with 10 points given to each variable for a total of 100 points. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence following discharge from hospital. The ten variables addressed in the Barthel scale are:
presence or absence of fecal incontinence presence or absence of urinary incontinence help needed with grooming help needed with toilet use help needed with feeding help needed with transfers (e.g. from chair to bed) help needed with walking help needed with dressing help needed with climbing stairs and help needed with bathing
- National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: 90 days ] [ Designated as safety issue: No ]
The NIHSS is a measure of neurologic deficit on a scale of 0-42, with 0 being normal. The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. The 11 items are:
Level of Consciousness Horizontal Eye Movement Visual field test Facial Palsy Motor Arm Motor Leg Limb Ataxia Sensory Language Speech Extinction and Inattention
|Study Start Date:||September 2007|
|Study Completion Date:||October 2010|
|Primary Completion Date:||October 2010 (Final data collection date for primary outcome measure)|
Experimental: Tier One
Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one ho.
Drug: Activated Protein C
Intravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset
Other Name: Xigris
An ischemic stroke occurs when there is damage to the brain caused by blockage in the blood vessels supplying the brain. Approximately 500,000 people in the United States experience this type of stroke each year. The only approved treatment for acute stroke is to attempt to dissolve the blood clot using t-PA (tissue plasminogen activator). This treatment must be given within 3 hours of symptom onset and is associated with a risk of brain hemorrhage (bleeding in the brain) of about 6% (6 in 100 patients).
Activated Protein C (APC) is a protein in the blood that is important in dissolving blood clots and reducing inflammation. Studies in animals suggest that APC may also protect brain cells from injury caused by a stroke. We are doing this study to determine if giving APC to individuals who have had a stroke will be safe and will reduce the damage to brain cells caused by the stroke. APC is currently approved by the Food and Drug Administration (FDA) for use in patients with severe, life-threatening infections.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00533546
|United States, California|
|University of California Irvine Medical Center|
|Orange, California, United States, 92868|
|United States, Illinois|
|Loyola University Medical Center|
|Maywood, Illinois, United States, 60153|
|United States, Missouri|
|Washington University--Barnes-Jewish Hospital|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Brooklyn, New York, United States, 11203|
|Maimonides Medical Center|
|Brooklyn, New York, United States, 11219|
|Mt. Sinai School of Medicine|
|New York, New York, United States, 10029|
|Rochester General Hospital|
|Rochester, New York, United States, 14621|
|University of Rochester|
|Rochester, New York, United States, 14642|
|United States, South Carolina|
|Palmetto Health Richland|
|Columbia, South Carolina, United States, 29203|
|Study Chair:||Curtis Benesch, MD, MPH||University of Rochester|