The Spot Sign for Predicting and Treating ICH Growth Study - Full Text View

Sponsored by:	National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by:	National Institute of Neurological Disorders and Stroke (NINDS)
ClinicalTrials.gov Identifier:	NCT00810888

Purpose

The purpose of this study is to determine if computed tomography angiography can predict which individuals with intracerebral hemorrhage will experience significant growth in the size of the hemorrhage. For individuals who are at high risk for hemorrhage growth, the study will compare the drug recombinant activated factor VII (rFVIIa) to placebo to determine the effect of rFVIIa on intracerebral hemorrhage growth.

Condition	Intervention	Phase
Intracerebral Hemorrhage	Drug: recombinant activated factor VII Drug: placebo	Phase II

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment, Efficacy Study
Official Title:	The Spot Sign for Predicting and Treating Intracerebral Hemorrhage Growth Study

Further study details as provided by National Institute of Neurological Disorders and Stroke (NINDS):

Primary Outcome Measures:

Life-threatening thromboembolic complications defined as development of (1) acute myocardial ischemia; (2) acute cerebral ischemia; and (3) acute pulmonary embolism [ Time Frame: through day 4 after completion of study drug ] [ Designated as safety issue: Yes ]
The rate of hematoma growth among spot sign positive subjects at 24 hours, comparing subjects treated with rFVIIa to those treated with placebo. Hematoma growth will be defined as a > 33% or > 6 cc increase in volume. [ Time Frame: at 24 hours ] [ Designated as safety issue: No ]
The sensitivity and specificity of the spot sign for predicting hematoma growth [ Time Frame: Baseline head CT scan within 5 hours, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Incidence of other potentially study drug related thromboembolic complications such as deep venous thrombosis and elevations in troponin not associated with ECG changes [ Time Frame: through day 4 after completion of study drug ] [ Designated as safety issue: Yes ]
Ninety-day outcomes among spot positive subjects, dichotomized as modified Rankin Scale score of 0-4 verses 5-6, comparing subjects treated with rFVIIa to those treated with placebo [ Time Frame: 90 days (+/- 7 days) from time of study enrollment ] [ Designated as safety issue: No ]
The positive and negative predictive values of the spot sign and the accuracy of the site investigators for correct identification of the spot sign as compared to a blinded study neuroradiologist. [ Time Frame: Baseline head CT scan within 5 hours, followed by a CT angiogram. Hematoma growth determined by comparison with a head CT scan performed at 24 hours. ] [ Designated as safety issue: No ]

Estimated Enrollment:	184
Study Start Date:	December 2008
Estimated Study Completion Date:	April 2013
Estimated Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (or determined to be CTA "spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive either rFVIIa at 80 mcg/kg or a placebo.	Drug: recombinant activated factor VII Participants will receive rFVIIa at 80 mcg/kg.
2: Placebo Comparator Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (or determined to be CTA "spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive either rFVIIa at 80 mcg/kg or a placebo.	Drug: placebo an inactive substance
3: No Intervention Participants with ICH who are determined by CTA not to be at high risk for hemorrhage growth (determined to be CTA "spot sign" negative) will be enrolled into a prospective observational group.

Detailed Description:

Intracerebral hemorrhage (ICH)—breakage of a blood vessel with bleeding in the brain—is a devastating form of stroke with a 40-50 percent fatality rate and no proven treatment. Because the majority of deaths from ICH occur within several days of the stroke, interventions for improving outcomes must occur early in the treatment course. Among the potentially modifiable determinants of ICH outcome, hematoma growth is a particularly attractive target for intervention and a major focus of this trial.

The purpose of this study is to determine if an imaging test called computed tomography angiography (CTA) can predict which individuals with ICH will experience significant growth in the size of the hemorrhage. Growth of the hemorrhage can cause additional injury and may worsen the outcome. For individuals who are at high risk for hemorrhage growth based on CTA results (i.e., a positive CTA "spot sign," evidence of contrast leakage within the hemorrhage), the study will compare the effects of a drug called recombinant activated factor VII (NovoSeven®) or rFVIIa with a placebo to determine which is better for reducing ICH growth.

The primary goals of this trial are (1) to determine the sensitivity and specificity of the CTA spot sign for predicting hematoma growth; (2) to determine the feasibility of using CTA to identify individuals with ICH who are at high risk of hematoma growth and to select study participants for randomization to treatment with rFVIIa or placebo; and (3) to determine the rate of hematoma growth among spot-positive individuals at 24 hours—comparing individuals treated with rFVIIa to those treated with placebo.

Approximately 184 persons with ICH will be enrolled in one of two study groups at 10 clinical sites across the United States and Canada. Participants with ICH who are determined by CTA to be at high risk for hemorrhage growth (CTA "spot sign" positive) will be randomized to receive either the active study medication, rFVIIa, at 80 mcg/kg, or to receive a placebo (an inactive substance). Participants with ICH who are determined by CTA not to be at high risk for hemorrhage growth (determined to be CTA "spot sign" negative) will be enrolled into a prospective observational group.

Duration of the study for participants is approximately 3 months.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Acute, spontaneous ICH (including bleeding in cerebellum) diagnosed by non-enhanced CT scan within five hours of symptom onset. (Time of onset is defined as the last time the patient was witnessed to be at baseline (i.e., subjects who have stroke symptoms upon awakening will be considered to have their onset at beginning of sleep)
For spot positive patients, dosing of study drug within 90 minutes of enrolling CT scan

Exclusion Criteria:

Time of symptom onset of ICH is unknown or more than five hours prior to baseline CT scan,
ICH secondary to known or suspected trauma, aneurysm, vascular malformation, hemorrhagic conversion of ischemic stroke, venous sinus thrombosis, thrombolytic treatment of any condition (e.g., myocardial infarction, cerebral infarction, etc.), CNS tumor or CNS infection
Brainstem location of hemorrhage (patients with cerebellar hemorrhage may be enrolled)
Serum creatinine > 1.4 mg/dl (123 μmol/L). Sites that currently perform CTA as standard of care for ICH will follow their standard procedures regarding renal insufficiency.
Known allergy to iodinated contrast media
Intravenous or intra-arterial administration of iodinated contrast media within the previous 24 hours of baseline CT scan
Known hereditary (e.g., hemophilia) or acquired hemorrhagic diathesis, coagulation factor deficiency, or anticoagulant therapy with INR > 1.2
Known or suspected thrombocytopenia (unless current platelet count documented above 50,000 / μl)
Unfractionated heparin use with abnormal PTT
Low-molecular weight heparin use within the previous 24 hours
GPIIb/IIIa antagonist use in the previous two weeks
Glasgow Coma Scale score < 8 at time of proposed enrollment
Pre-admission modified Rankin Scale score > 2
Baseline ICH volume of < 0.5 cc (Hematoma volume will be estimated by local investigators from the baseline CT using the ABC / 2 method.)
Baseline ICH volume of > 90 cc
Planned surgical evacuation of ICH within 24 hours of symptom onset (Placement of intraventricular catheter is not a contraindication to study enrollment.)
Recent (within 90 days) myocardial infarction, coronary artery bypass surgery, unstable angina, transient ischemic attack, ischemic stroke, cerebral bypass surgery, carotid endarterectomy, deep venous thrombosis, pulmonary embolism, or coronary or cerebrovascular angioplasty or stenting
Baseline electrocardiogram shows evidence of acute cardiac ischemia (ST elevation in two contiguous leads, new LBBB, or ST depression)
Clinical history suggestive of acute cardiac ischemia (e.g., chest pain)
Abnormal baseline troponin
Pregnancy or lactating
Advanced or terminal illness or any other condition the investigator feels would pose a significant hazard to the patient if rFVIIa were administered
Recent (within 30 days) participation in any investigational drug or device trial or earlier participation in any investigational drug or device trial for which the duration of effect is expected to persist until the time of STOP-IT enrollment
Planned withdrawal of care or comfort care measures

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810888

Contacts

Contact: Janice A. Carrozzella, RN, BA, RT(R)

513-475-8793

Janice.carrozzella@uc.edu

Locations

United States, California
University of California, San Diego
San Diego, California, United States, 92103
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Nevada
Sunrise Medical Center
Las Vegas, Nevada, United States, 89169
United States, New York
Columbia University
New York, New York, United States, 10032
United States, Ohio
University of Cincinnati—Clinical Coordinating Center
Cincinnati, Ohio, United States, 45267-0525
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104-4283
University of Site PIttsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
University of Texas
Houston, Texas, United States, 77030
Canada, Alberta
University of Calgary
Calgary, Alberta, Canada, T2N2T9
Canada, Ontario
Sunnybrook Health Science Center
Toronto, Ontario, Canada, M4N3M5

Sponsors and Collaborators

National Institute of Neurological Disorders and Stroke (NINDS)

Investigators

Principal Investigator:	Matthew L. Flaherty, MD	University of Cincinnati
Principal Investigator:	Edward C. Jauch, MD, MS	Primary Emergency Medicine Investigator, Medical University of South Carolina

More Information

trial website This link exits the ClinicalTrials.gov site

Responsible Party:	University of Cincinnati ( Matthew L. Flaherty, MD, Principal Investigator )
Study ID Numbers:	P50NS044283_STOP_IT, 2P50NS044283-06
Study First Received:	December 15, 2008
Last Updated:	December 17, 2008
ClinicalTrials.gov Identifier:	NCT00810888
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Neurological Disorders and Stroke (NINDS):

intracerebral hemorrhage
ICH
computed tomography angiography
CTA

recombinant activated factor seven
rFVIIa
NovoSeven
recombinant activated factor VII

Study placed in the following topic categories:

Cerebral Hemorrhage
Vascular Diseases
Central Nervous System Diseases
Intracranial Hemorrhages

Brain Diseases
Hemorrhage
Cerebrovascular Disorders

Additional relevant MeSH terms:

Pathologic Processes
Nervous System Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 14, 2009