Activated Protein C in Acute Stroke Trial

NCT ID: NCT00533546

Last Updated: 2016-10-24

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2010-10-31

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.

Conditions

Stroke

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Activated Protein C

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Xigris

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Rochester

OTHER

Sponsor Role: lead

Responsible Party

Curtis Benesch

Associate Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Curtis Benesch, MD, MPH

Role: STUDY_CHAIR

University of Rochester

Locations

University of California Irvine Medical Center

Orange, California, United States

Loyola University Medical Center

Maywood, Illinois, United States

Washington University--Barnes-Jewish Hospital

St Louis, Missouri, United States

SUNY Downstate

Brooklyn, New York, United States

Maimonides Medical Center

Brooklyn, New York, United States

Mt. Sinai School of Medicine

New York, New York, United States

Rochester General Hospital

Rochester, New York, United States

University of Rochester

Rochester, New York, United States

Palmetto Health Richland

Columbia, South Carolina, United States

Countries

United States

Other Identifiers

5R01HL080107

Identifier Type: NIH

Identifier Source: secondary_id

View Link

5R01HL080107-05

Identifier Type: NIH

Identifier Source: secondary_id

View Link

537

Identifier Type: -

Identifier Source: org_study_id