Activated Protein C in Acute Stroke Trial

Stroke Clinical Trial

— APCAST  

Official title:

Activated Protein C in Acute Stroke Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00533546
• Other study ID #: 537
• Secondary ID: 5R01HL080107-05
• Status: Terminated
• Phase: Phase 2
• First received: September 19, 2007
• Last updated: December 10, 2010
• Start date: September 2007
• Est. completion date: December 2010

Study information

• Verified date: December 2010
• Source: National Heart, Lung, and Blood Institute (NHLBI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 72
• Est. completion date: December 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Stroke

Intervention

Drug:
• Activated Protein C
Intravenous APC (10, 15, 22, 33, 50, and 75 g/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset

Locations

Country	Name	City	State
United States	Maimonides Medical Center	Brooklyn	New York
United States	SUNY Downstate	Brooklyn	New York
United States	Palmetto Health Richland	Columbia	South Carolina
United States	Loyola University Medical Center	Maywood	Illinois
United States	Mt. Sinai School of Medicine	New York	New York
United States	University of California Irvine Medical Center	Orange	California
United States	Rochester General Hospital	Rochester	New York
United States	University of Rochester	Rochester	New York
United States	Washington University--Barnes-Jewish Hospital	St. Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of major intracranial hemorrhage (fatal and non-fatal)		Measured within 36-48 hours of treatment	Yes
Secondary	Rates of other adverse events, rates of neurological deterioration, functional outcomes, pharmacokinetic analyses, changes in blood and laboratory findings		Measured at 90 days	Yes