Activated Protein C in Acute Stroke Trial

NCT00533546 | Terminated Phase 2 Results DMC

• 3 other identifiers: 5375R01HL0801075R01HL080107-05
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 9

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.

Conditions

Stroke

Keywords

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Intracranial Hemorrhage

  Intracranial Hemorrhage (ICH): Fatal ICH: Death ascribed to ICH confirmed by autopsy or CT imaging. Major non-fatal ICH: Hemorrhage within brain parenchyma associated with neurological deterioration or evidence of subdural, epidural or intraventricular hemorrhage on CT imaging, with or without symptoms. Symptomatic ICH: Hemorrhage within the territory of qualifying infarction with neurological deterioration as measured by \> 2 point increase in the National Institutes of Health Stroke Scale (NIHSS) from previous examination; hemorrhage in different vascular territory associated with new neurologic deficit. All symptomatic ICH will be defined as a major ICH. Asymptomatic ICH: Presence of hemorrhage within the territory of qualifying infarction without neurological deterioration ascribed to the hemorrhage or presence of hemorrhage within brain parenchyma outside the territory of qualifying infarction without new neurologic deficit (would not be considered a major ICH)

  Measured within 36-48 hours of treatment

Secondary Outcomes (3)

• Mean Modified Rankin Scale Score

  90 days

• Mean Barthel Index Score

  90 days

• National Institutes of Health Stroke Scale (NIHSS)

  90 days

Study Arms (1)

Tier One

EXPERIMENTAL

Participants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one ho.

Drug: Activated Protein C

Interventions

Activated Protein C 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

Also known as: Xigris

Tier One

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Rochester: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (9)

University of California Irvine Medical Center

Orange, California, 92868, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Washington University--Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

SUNY Downstate

Brooklyn, New York, 11203, United States

Location

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Mt. Sinai School of Medicine

New York, New York, 10029, United States

Location

Rochester General Hospital

Rochester, New York, 14621, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Palmetto Health Richland

Columbia, South Carolina, 29203, United States

Location

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Interventions

Protein C; drotrecogin alfa activated

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Glycoproteins; Glycoconjugates; Carbohydrates; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Blood Coagulation Factor Inhibitors; Biological Factors

Limitations and Caveats

Study was terminated after completion of Tier One dosing level (n=12 subjects) due to lack of recruitment.

Results Point of Contact

• Title: Curtis Benesch, M.D., M.P.H.
• Organization: University of Rochester

curtis_benesch@urmc.rochester.edu

585 275-2530

Study Officials

• Curtis Benesch, MD, MPH

  University of Rochester

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: September 19, 2007
• First Posted: September 21, 2007
• Study Start: September 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: October 1, 2010
• Last Updated: October 24, 2016
• Results First Posted: October 24, 2016

Record last verified: 2016-09

Locations

US (9)