Activated Protein C in Acute Stroke Trial (APCAST)

This study has been terminated.
(Lack of recruitment)
Sponsor:
Information provided by:
National Heart, Lung, and Blood Institute (NHLBI)
ClinicalTrials.gov Identifier:
NCT00533546
First received: September 19, 2007
Last updated: December 10, 2010
Last verified: December 2010
  Purpose

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.


Condition Intervention Phase
Stroke
Drug: Activated Protein C
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Activated Protein C in Acute Stroke Trial

Resource links provided by NLM:


Further study details as provided by National Heart, Lung, and Blood Institute (NHLBI):

Primary Outcome Measures:
  • Occurrence of major intracranial hemorrhage (fatal and non-fatal) [ Time Frame: Measured within 36-48 hours of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Rates of other adverse events, rates of neurological deterioration, functional outcomes, pharmacokinetic analyses, changes in blood and laboratory findings [ Time Frame: Measured at 90 days ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 72
Study Start Date: September 2007
Estimated Study Completion Date: December 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants will receive APC by intravenous injection.
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
Other Name: Xigris

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00533546

Locations
United States, California
University of California Irvine Medical Center
Orange, California, United States, 92868
United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Missouri
Washington University--Barnes-Jewish Hospital
St. Louis, Missouri, United States, 63110
United States, New York
Maimonides Medical Center
Brooklyn, New York, United States, 11219
SUNY Downstate
Brooklyn, New York, United States, 11203
Mt. Sinai School of Medicine
New York, New York, United States, 10029
University of Rochester
Rochester, New York, United States, 14642
Rochester General Hospital
Rochester, New York, United States, 14621
United States, South Carolina
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
Sponsors and Collaborators
Investigators
Study Chair: Curtis Benesch, MD, MPH University of Rochester
  More Information

No publications provided

Responsible Party: Curtis Benesch, MD, MPH, University of Rochester
ClinicalTrials.gov Identifier: NCT00533546     History of Changes
Other Study ID Numbers: 537, 5R01HL080107-05
Study First Received: September 19, 2007
Last Updated: December 10, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by National Heart, Lung, and Blood Institute (NHLBI):
Acute Ischemic Stroke

Additional relevant MeSH terms:
Cerebral Infarction
Stroke
Brain Diseases
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Nervous System Diseases
Vascular Diseases
Protein C
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014