on November 29, 2004
Published online before print November 29, 2004, doi: 10.1161/01.STR.0000149628.80251.b8
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Submitted on July 6, 2004
From the Departments of Neurology and Neurosurgery (S.M.), Columbia University College of Physicians and Surgeons, New York, NY; Novo Nordisk A/S (N.B.), Bagsvaerd, Denmark; the University of Cincinnati Medical Center (J.B.), Cincinnati, Ohio; Royal Melbourne Hospital (S.D.), University of Melbourne, Melbourne, Australia; Washington University School of Medicine (M.D.), St. Louis, Mo; Novo Nordisk (B.S.), Princeton, NY; and the University of Heidelberg (T.S.), Heidelberg, Germany. * To whom correspondence should be addressed. E-mail: sam14{at}columbia.edu.
Background and Purpose--Hematoma growth occurs in 38% of intracerebral hemorrhage (ICH) patients scanned by computed tomography (CT) within 3 hours of onset. Activated recombinant factor VIIa (rFVIIa) promotes hemostasis at sites of vascular injury and may minimize hematoma growth after ICH. Methods--In this randomized, double-blind, placebo-controlled, dose-escalation trial, 48 subjects with ICH diagnosed within 3 hours of onset were treated with placebo (n=12) or rFVIIa (10, 20, 40, 80, 120, or 160 µg/kg; n=6 per group). The primary endpoint was the frequency of adverse events (AEs). Safety assessments included serial electrocardiography (ECG), troponin I and coagulation testing, lower extremity Doppler ultrasonography, and calculation of edema:ICH volume ratios. Results--Mean age was 61 years (range, 30 to 93) and 57% were male. At admission, mean National Institutes of Health Stroke Scale (NIHSS) score was 14 (range, 1 to 26), median Glasgow Coma Scale score was 14 (range, 6 to 15), and mean ICH volume was 21 mL (range, 1 to 151). Mean time from onset to treatment was 181 minutes (range, 120 to 265). Twelve serious AEs occurred, including 5 deaths (mortality 11%). Six AEs were considered possibly treatment-related, including rash, vomiting, fever, ECG T-wave inversion, and 2 cases of deep vein thrombosis (placebo and 20-µg/kg groups). No myocardial ischemia, consumption coagulopathy, or dose-related increase in edema:ICH volume occurred. Conclusion--This small phase II trial evaluated a wide range of rFVIIa doses in acute ICH and raised no major safety concerns. Larger studies are justified to determine whether rFVIIa can safely and effectively limit ICH growth.
Accepted on July 22, 2004
Safety and Feasibility of Recombinant Factor VIIa for Acute Intracerebral Hemorrhage
Stephan A. Mayer MD*;
Key words: cerebral hemorrhage • coagulation • emergency medical services • fibrinolysis • stroke
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