Activated Protein C in Acute Stroke Trial (APCAST)

University of Rochester

Status and phase

Terminated

Phase 2

Conditions

Stroke

Treatments

Drug: Activated Protein C

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00533546

5R01HL080107-05 (U.S. NIH Grant/Contract)

537

5R01HL080107 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

12 patients

Sex

All

Ages

18+ years old

Volunteers

No 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)