Intracerebral hemorrhage (ICH) is conservatively estimated to affect 67,000 persons in the United States and 5,000 persons in Canada annually and is associated with a 40-50% case-fatality rate. There are no proven, effective treatments for ICH. The demonstration that hematoma growth after ictus is common and associated with neurological decline has spurred research into early hemostatic therapy to potentially improve patient outcomes. Recombinant activated factor VII (rFVIIa) was proven to reduce hematoma growth when administered within four hours of symptom onset in two randomized, blinded, placebocontrolled trials. While clinical outcomes were improved in a phase lib trial, they were not improved in a phase III trial of this drug. Because rFVIIa works to stop bleeding but should not otherwise affect the natural history of ICH, only patients destined to have hematoma growth will benefit from this therapy. Ideally, clinicians will be able to identify patients who will have significant hematoma growth regardless of their time to presentation and administer hemostatic therapy to this group. CT angiography (CTA) has shown promise for predicting hematoma growth. In recent retrospective case series patients with contrast leakage within their hematomas during CTA (the spot sign) had greater risk of subsequent hematoma growth than patients without leakage. The next logical step in this treatment paradigm is to prospectively confirm the ability of CTA to predict hematoma growth and to explore the role CTA may play in treatment allocation. The proposed phase II study will enroll patients with ICH less than six hours from symptom onset. Patients will be included in one of two study arms. The first arm will be a multicenter, randomized, double-blind, placebo-controlled trial comparing rFVIIa to placebo for treatment of patients with a spot sign on CTA. The second arm will be a multicenter, prospective, observational study of hematoma growth among patients without a spot sign on CTA. The goals of this study are to establish the usefulness of CTA for predicting hematoma growth, to determine the accuracy of non-radiologists at identifying the spot sign, to demonstrate the feasibility of using CTA in the acute setting in a randomized treatment trial, and to provide preliminary efficacy data for rFVIIa treatment in this setting. If the current study goals are met the next step will be a phase III trial designed to show clinical benefit among ICH patients with a spot sign who are treated with rFVIIa (versus placebo) within six hours of symptom onset.
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