Intracerebral Hemorrhage | The Spot Sign for Predicting and Treating ICH Growth Study
Intracerebral Hemorrhage research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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) - Age >/= 18 years through 80 years (candidates must have had their 18th birthday, but not had their 81st birthday) - 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.), central nervous system (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 international normalized ration (INR) > 1.2 - Known or suspected thrombocytopenia (unless current platelet count documented above 50,000 / μl) - Unfractionated heparin use with abnormal partial thromboplastin time (PTT) - Low-molecular weight heparin use within the previous 24 hours - GPIIb/IIIa antagonist use in the previous two weeks - Direct thrombin inhibitor or factor Xa inhibitor within the previous 48 hours - 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.) - Evidence of acute or subacute ischemic stroke on baseline qualifying CT scan - Clinical history of thromboembolism or ischemic vascular disease, including myocardial infarction, coronary artery bypass surgery, cardiac angina, transient ischemic attack, ischemic stroke, peripheral artery disease (vascular claudication), cerebral bypass surgery, carotid endarterectomy, deep venous thrombosis, pulmonary embolism, or coronary or cerebrovascular angioplasty or stenting. (Clinically silent evidence of old ischemia on EKG (Q waves) or CT scan (silent old infarct) will not be considered reasons for exclusion.) - Baseline electrocardiogram shows evidence of acute cardiac ischemia (ST elevation in two contiguous leads, new left bundle branch block (LBBB), or ST depression) - Clinical history suggestive of acute cardiac ischemia (e.g., chest pain) - Abnormal baseline troponin - Females of childbearing potential who are known to be pregnant and/or lactating or who have positive pregnancy tests on admission - 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 - Patient known or suspected of not being able to comply with trial protocol (e.g., due to alcoholism, drug dependency or psychological disorder) - Informed consent cannot be obtained from the patient or legally authorized representative
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:recombinant activated factor VIIParticipants will receive rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).
Drug:placeboAn inactive substance (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg)
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Group 1-Recombinant activated factor VIIParticipants with ICH determined by CTA to be high risk for hemorrhage growth ("spot sign" positive for contrast leakage within the brain hematoma) randomized to receive rFVIIa at 80 mcg/kg (max dose 21.3 mL).
Group 2 - PlaceboParticipants with ICH determined by CTA to be high risk for hemorrhage growth ("spot sign" positive for contrast leakage within the brain hematoma) will be randomized to receive placebo.
Group 3 - Observation Only ArmParticipants with ICHdetermined by CTA not to be at high risk for hemorrhage growth (CTA "spot sign" negative) enrolled into a prospective observational group.
Start Date: November 2010
Completed Date: April 2016
Phase: Phase 2
Primary Outcome: Number of Study Subjects With Life-threatening Thromboembolic Complications
Secondary Outcome: Number of Participants With Other Potentially Study Drug Related Thromboembolic Complications Such as Deep Venous Thrombosis (DVT) and Elevations in Troponin Not Associated With ECG Changes
Study sponsors, principal investigator, and references
Principal Investigator: Matthew L. Flaherty, MD
Lead Sponsor: University of Cincinnati
Collaborator: National Institute of Neurological Disorders and Stroke (NINDS)