The Spot Sign for Predicting and Treating ICH Growth Study
Condition: Intracerebral Hemorrhage
MeSH terms: Cerebral Hemorrhage; Hemorrhage
Intervention: recombinant activated factor VII; placebo
Intervention description: Participants will receive rFVIIa at 80 mcg/kg (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg).; An inactive substance (maximum dose volume 21.3 mL, equivalent to maximum weight of 160 kg)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 92.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: intracerebral hemorrhage; ICH; computed tomography angiography; CTA; recombinant activated factor seven; rFVIIa; NovoSeven; recombinant activated factor VII

Summary:

      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.
    

Eligibility 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)

          -  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