search
Back to results

Activated Protein C in Acute Stroke Trial (APCAST)

Primary Purpose

Stroke

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Activated Protein C
Sponsored by
University of Rochester
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Stroke focused on measuring Acute Ischemic Stroke

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Symptoms of acute ischemic stroke; acute ischemic stroke is defined as the sudden onset of a measurable neurological deficit presumably attributable to focal cerebral ischemia, and otherwise not attributable to ICH or other disease process
  • Symptom onset within 0-9 hours of administration of study medication Stroke onset is defined as the time of first symptoms or signs of neurologic deficit. If the onset of symptoms/signs is unwitnessed, time of onset is presumed to be the last time the patient was observed to be intact
  • Neurologic deficit on examination with NIHSS of greater than 4 and less than 23
  • In women of childbearing potential, a negative urine pregnancy test prior to enrollment (to be confirmed later by serum test)
  • Signed informed consent by subject or authorized representative

Exclusion Criteria:

  • Computed tomography scan of the brain with evidence of intracranial hemorrhage or any finding not consistent with acute ischemic stroke as cause of presenting symptoms
  • CT imaging demonstrating hypodensity more than 1/3 of MCA territory or mass effect
  • Neurological (other than presenting stroke) or psychiatric condition that may affect the patient's functional status or that may interfere with the patient's assessment
  • Clinically relevant pre-existing neurological deficit (historical modified Rankin score greater than 2 regardless of cause)
  • Treatment with tissue plasminogen activator or other thrombolytic agent within 3 months, including treatment with tissue plasminogen activator for current stroke
  • Need for treatment with anti-platelet agent or anticoagulant within 36 hours
  • Previous stroke or serious head trauma within 3 months
  • Major surgery within previous 14 days
  • History of intracranial hemorrhage
  • Rapidly improving or minor symptoms
  • Symptoms suggestive of subarachnoid hemorrhage
  • Gastrointestinal hemorrhage or urinary tract hemorrhage within previous 21 days
  • Arterial puncture at noncompressible site within the previous 7 days
  • Seizure at onset of stroke
  • Use of oral anticoagulant medications at time of symptom onset or treatment with subcutaneous or intravenous heparin within previous 48 hours with elevated partial thromboplastin time
  • INR values greater than 1.5
  • Platelet count less than 100,000/μL
  • Glucose concentration less than 40 mg/dL or greater than 400mg/dL
  • Participation in another clinical trial within the last 30 days, or planned participation in another clinical trial
  • Women who are currently breast-feeding
  • Known resistance to activated Protein C (Factor V Leiden mutation)

Sites / Locations

  • University of California Irvine Medical Center
  • Loyola University Medical Center
  • Washington University--Barnes-Jewish Hospital
  • SUNY Downstate
  • Maimonides Medical Center
  • Mt. Sinai School of Medicine
  • Rochester General Hospital
  • University of Rochester
  • Palmetto Health Richland

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Tier One

Arm Description

Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one ho.

Outcomes

Primary Outcome Measures

Number of Participants With Intracranial Hemorrhage
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)

Secondary Outcome Measures

Mean Modified Rankin Scale Score
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
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)
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

Full Information

First Posted
September 19, 2007
Last Updated
September 1, 2016
Sponsor
University of Rochester
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00533546
Brief Title
Activated Protein C in Acute Stroke Trial
Acronym
APCAST
Official Title
Activated Protein C in Acute Stroke Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Terminated
Why Stopped
Lack of recruitment
Study Start Date
September 2007 (undefined)
Primary Completion Date
October 2010 (Actual)
Study Completion Date
October 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Rochester
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this research study is to determine the safety and learn more about the dose of Activated Protein C (APC) in reducing the damage from stroke.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke
Keywords
Acute Ischemic Stroke

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Tier One
Arm Type
Experimental
Arm Description
Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one ho.
Intervention Type
Drug
Intervention Name(s)
Activated Protein C
Other Intervention Name(s)
Xigris
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of Participants With Intracranial Hemorrhage
Description
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)
Time Frame
Measured within 36-48 hours of treatment
Secondary Outcome Measure Information:
Title
Mean Modified Rankin Scale Score
Description
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.
Time Frame
90 days
Title
Mean Barthel Index Score
Description
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
Time Frame
90 days
Title
National Institutes of Health Stroke Scale (NIHSS)
Description
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
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Symptoms of acute ischemic stroke; acute ischemic stroke is defined as the sudden onset of a measurable neurological deficit presumably attributable to focal cerebral ischemia, and otherwise not attributable to ICH or other disease process Symptom onset within 0-9 hours of administration of study medication Stroke onset is defined as the time of first symptoms or signs of neurologic deficit. If the onset of symptoms/signs is unwitnessed, time of onset is presumed to be the last time the patient was observed to be intact Neurologic deficit on examination with NIHSS of greater than 4 and less than 23 In women of childbearing potential, a negative urine pregnancy test prior to enrollment (to be confirmed later by serum test) Signed informed consent by subject or authorized representative Exclusion Criteria: Computed tomography scan of the brain with evidence of intracranial hemorrhage or any finding not consistent with acute ischemic stroke as cause of presenting symptoms CT imaging demonstrating hypodensity more than 1/3 of MCA territory or mass effect Neurological (other than presenting stroke) or psychiatric condition that may affect the patient's functional status or that may interfere with the patient's assessment Clinically relevant pre-existing neurological deficit (historical modified Rankin score greater than 2 regardless of cause) Treatment with tissue plasminogen activator or other thrombolytic agent within 3 months, including treatment with tissue plasminogen activator for current stroke Need for treatment with anti-platelet agent or anticoagulant within 36 hours Previous stroke or serious head trauma within 3 months Major surgery within previous 14 days History of intracranial hemorrhage Rapidly improving or minor symptoms Symptoms suggestive of subarachnoid hemorrhage Gastrointestinal hemorrhage or urinary tract hemorrhage within previous 21 days Arterial puncture at noncompressible site within the previous 7 days Seizure at onset of stroke Use of oral anticoagulant medications at time of symptom onset or treatment with subcutaneous or intravenous heparin within previous 48 hours with elevated partial thromboplastin time INR values greater than 1.5 Platelet count less than 100,000/μL Glucose concentration less than 40 mg/dL or greater than 400mg/dL Participation in another clinical trial within the last 30 days, or planned participation in another clinical trial Women who are currently breast-feeding Known resistance to activated Protein C (Factor V Leiden mutation)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Curtis Benesch, MD, MPH
Organizational Affiliation
University of Rochester
Official's Role
Study Chair
Facility Information:
Facility Name
University of California Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
Loyola University Medical Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Washington University--Barnes-Jewish Hospital
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
SUNY Downstate
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Maimonides Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11219
Country
United States
Facility Name
Mt. Sinai School of Medicine
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Rochester General Hospital
City
Rochester
State/Province
New York
ZIP/Postal Code
14621
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Palmetto Health Richland
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Activated Protein C in Acute Stroke Trial

We'll reach out to this number within 24 hrs