Intracerebral hemorrhage (ICH) is conservatively estimated to affect 67,000 persons in the United States and5,000 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 andassociated with neurological decline has spurred research into early hemostatic therapy to potentiallyimprove patient outcomes. Recombinant activated factor VII (rFVIIa) was proven to reduce hematomagrowth when administered within four hours of symptom onset in two randomized, blinded, placebocontrolledtrials. While clinical outcomes were improved in a phase lib trial, they were not improved in aphase III trial of this drug. Because rFVIIa works to stop bleeding but should not otherwise affect the naturalhistory 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 timeto presentation and administer hemostatic therapy to this group.CT angiography (CTA) has shown promise for predicting hematoma growth. In recent retrospective caseseries patients with contrast leakage within their hematomas during CTA (the spot sign) had greater risk ofsubsequent hematoma growth than patients without leakage. The next logical step in this treatmentparadigm is to prospectively confirm the ability of CTA to predict hematoma growth and to explore the roleCTA may play in treatment allocation. The proposed phase II study will enroll patients with ICH less than sixhours from symptom onset. Patients will be included in one of two study arms. The first arm will be amulticenter, randomized, double-blind, placebo-controlled trial comparing rFVIIa to placebo for treatment ofpatients with a spot sign on CTA. The second arm will be a multicenter, prospective, observational study ofhematoma growth among patients without a spot sign on CTA. The goals of this study are to establish theusefulness of CTA for predicting hematoma growth, to determine the accuracy of non-radiologists atidentifying the spot sign, to demonstrate the feasibility of using CTA in the acute setting in a randomizedtreatment trial, and to provide preliminary efficacy data for rFVIIa treatment in this setting. If the currentstudy goals are met the next step will be a phase III trial designed to show clinical benefit among ICHpatients with a spot sign who are treated with rFVIIa (versus placebo) within six hours of symptom onset.
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