StrokePhase 2APCASTNCT00533546
Activated Protein C in Acute Stroke Trial
A Phase 2 study testing Activated Protein C in people with Stroke, run by University of Rochester at 9 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Activated Protein C
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 9 sitesUnited States
- Study dates
- Sep 2007to Oct 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 21Show fewer
- 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)
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
SUNY Downstate
Brooklyn, New York, 11203
Maimonides Medical Center
Brooklyn, New York, 11219
Palmetto Health Richland
Columbia, South Carolina, 29203
Loyola University Medical Center
Maywood, Illinois, 60153
Mt. Sinai School of Medicine
New York, New York, 10029
University of California Irvine Medical Center
Orange, California, 92868
Rochester General Hospital
Rochester, New York, 14621
University of Rochester
Rochester, New York, 14642
Washington University--Barnes-Jewish Hospital
St Louis, Missouri, 63110
About this study
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.
Read the 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
- Being tested
- Activated Protein C
- Keywords
- Acute Ischemic Stroke
- Medical subject headings
- Stroke, Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Activated Protein CDrug
Also called Xigris
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Activated Protein C |
What is being measured
The primary outcome is the main question the study is designed to answer.
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: Measured within 36-48 hours of treatment
Secondary outcomes (3)
Mean Modified Rankin Scale Score
Measure of disability as determined by categorical assignment on modified Rankin Scale.. The modified Rankin Scale (mRS) is a commonly used scale for measuring the degree of disability or dependence in the daily activities of people who have suffered a stroke or other causes of neurological disability.
The scale runs from 0-6, running from perfect health without symptoms to death.
0 - No symptoms.
- - No significant disability. Able to carry out all usual activities, despite some symptoms.
- - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities.
- - Moderate disability. Requires some help, but able to walk unassisted.
- - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted.
- - Severe disability. Requires constant nursing care and attention, bedridden, incontinent.
- - Dead.
Measured: 90 days
Mean Barthel Index Score
Measure of functional recovery using Barthel Index (range 0-100). The Barthel scale or Barthel ADL index is an ordinal scale used to measure performance in activities of daily living (ADL). Each performance item is rated on this scale with a given number of points assigned to each level or ranking. It uses ten variables describing ADL and mobility with 10 points given to each variable for a total of 100 points. A higher number is associated with a greater likelihood of being able to live at home with a degree of independence following discharge from hospital. The ten variables addressed in the Barthel scale are:
presence or absence of fecal incontinence presence or absence of urinary incontinence help needed with grooming help needed with toilet use help needed with feeding help needed with transfers (e.g. from chair to bed) help needed with walking help needed with dressing help needed with climbing stairs and help needed with bathing
Measured: 90 days
National Institutes of Health Stroke Scale (NIHSS)
The NIHSS is a measure of neurologic deficit on a scale of 0-42, with 0 being normal. The National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) is a tool used by healthcare providers to objectively quantify the impairment caused by a stroke. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0. The 11 items are:
Level of Consciousness Horizontal Eye Movement Visual field test Facial Palsy Motor Arm Motor Leg Limb Ataxia Sensory Language Speech Extinction and Inattention
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2007 (estimated)
- Study startSep 2007
- Primary completionOct 2010
- Study completionOct 2010
Why it stopped: Lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Curtis Benesch, University of Rochester
- Investigators
- Curtis Benesch, MD, MPH, Study chair, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00533546
- Sponsor's protocol ID
- 537
- Other IDs
- 5R01HL080107, 5R01HL080107-05
- Acronym
- APCAST
- Status last verified
- Sep 2016
- First submitted
- 19 Sep 2007
- Last updated
- 24 Oct 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Activated Protein C in Acute Stroke Trial
- ClinicalTrials.gov ID
- NCT00533546
- Acronym / sponsor ID
- APCAST / 537
- Conditions
- Stroke
- Keywords
- Acute Ischemic Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of recruitment
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Sep 2007
- Primary completion
- Oct 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 21 Sep 2007 (estimated)
- Results
- Posted 24 Oct 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tier One | Experimental | Drug: Activated Protein CParticipants will receive APC by intravenous injection, receiving 50% of dose as a bolus and the remainder as an infusion over one ho. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Activated Protein CAlso: XigrisIntravenous APC (10, 15, 22, 33, 50, and 75 mcg/kg) administered to patients with acute ischemic stroke within 0 - 9 hours of symptom onset | Drug | Tier One |
Primary outcome
Number of Participants With Intracranial Hemorrhage
Time frame: Measured within 36-48 hours of treatment
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)
3 secondary outcomes
Mean Modified Rankin Scale Score
Time frame: 90 days
Mean Barthel Index Score
Time frame: 90 days
National Institutes of Health Stroke Scale (NIHSS)
Time frame: 90 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Curtis Benesch, MD, MPH study chair
University of Rochester
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Activated Protein C in people with Stroke, run by University of Rochester at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Oct 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Intracranial Hemorrhage (time frame: Measured within 36-48 hours of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Oct 2016.