Clinical trial NCT00533546: Activated Protein C in Acute Stroke Trial
Official title: Activated Protein C in Acute Stroke Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Stroke
Keywords: Acute Ischemic Stroke
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-09-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Number of Participants With Intracranial Hemorrhage
timeFrame: Measured within 36-48 hours of treatment
Secondary outcomes:
measure: Mean Modified Rankin Scale Score
timeFrame: 90 days
measure: Mean Barthel Index Score
timeFrame: 90 days
measure: National Institutes of Health Stroke Scale (NIHSS)
timeFrame: 90 days
Other outcomes:
Locations:
city: Orange
country: United States
facility: University of California Irvine Medical Center
state: California
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: St. Louis
country: United States
facility: Washington University--Barnes-Jewish Hospital
state: Missouri
city: Brooklyn
country: United States
facility: SUNY Downstate
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: New York
country: United States
facility: Mt. Sinai School of Medicine
state: New York
city: Rochester
country: United States
facility: Rochester General Hospital
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
Study officials:
affiliation: University of Rochester
name: Curtis Benesch, MD, MPH
role: STUDY_CHAIR
References: