BACKGROUND AND PURPOSE: Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven) for preventing early hematoma growth in acute ICH. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated withplacebo or 5, 20, 40, or 80 microg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs). RESULTS: Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred. CONCLUSIONS: Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.
RCT Entities:
BACKGROUND AND PURPOSE: Ultra-early hemostatic therapy may improve outcome after intracerebral hemorrhage (ICH) by preventing rebleeding and hematoma expansion. We conducted this trial to evaluate the safety of activated recombinant factor VII (rFVIIa; NovoSeven) for preventing early hematoma growth in acute ICH. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial, 40 patients diagnosed with ICH by computed tomography within 3 hours of onset were treated with placebo or 5, 20, 40, or 80 microg/kg of rFVIIa ( n = 8 per group). Patients with any history of thromboembolic or vaso-occlusive disease were excluded. The primary endpoint was the frequency of adverse events (AEs). RESULTS: Mean age was 65 years (range 34 - 91) and the median admission Glasgow Coma Scale score was 14.5 (range 6 to 15). Mean ICH volume was 17 +/- 19 mL; nearly three-quarters were located in the basal ganglia ( n = 29). The mean interval from onset to treatment was 178 +/- 41 minutes. Thirty-three patients experienced 186 AEs, which occurred with similar frequency in the five groups. There were 10 thromboembolic AEs, including one case of deep vein thrombosis (20 microg g/kg group); one case of cerebral infarction (placebo); two cases of pulmonary embolism (20 and 40 microg g/kg groups); and six instances of ischemic ECG changes or cardiac enzyme elevation (placebo [ n = 2], 20 microg g/kg [ n = 1], 40 microg g/kg [ n = 1], and 80 microg g/kg [ n = 2] groups). No consumption coagulopathy or dose-related increase in edema-to-ICH volume ratio occurred. CONCLUSIONS: Ultra-early rFVIIa treatment for ICH was associated with a reasonable safety profile in this preliminary study across a wide range of dosages. Further research is warranted to investigate the safety and potential efficacy of rFVIIa for minimizing ICH growth.
Authors: Philip W Friederich; Christiaan P Henny; Embert J Messelink; Mark G Geerdink; Tymen Keller; Karl-Heinz Kurth; Harry R Büller; Marcel Levi Journal: Lancet Date: 2003-01-18 Impact factor: 79.321
Authors: B G Macik; C M Lindley; J Lusher; W T Sawyer; A L Bloom; J F Harrison; K Baird-Cox; K Birch; S Glazer; H R Roberts Journal: Blood Coagul Fibrinolysis Date: 1993-08 Impact factor: 1.276
Authors: Joshua N Goldstein; Louis E Fazen; Lauren Wendell; Yuchiao Chang; Natalia S Rost; Ryan Snider; Kristin Schwab; Rishi Chanderraj; Christopher Kabrhel; Catherine Kinnecom; Emilie Fitzmaurice; Eric E Smith; Steven M Greenberg; Jonathan Rosand Journal: Neurocrit Care Date: 2008-09-23 Impact factor: 3.210
Authors: Veronica Yank; C Vaughan Tuohy; Aaron C Logan; Dena M Bravata; Kristan Staudenmayer; Robin Eisenhut; Vandana Sundaram; Donal McMahon; Ingram Olkin; Kathryn M McDonald; Douglas K Owens; Randall S Stafford Journal: Ann Intern Med Date: 2011-04-19 Impact factor: 25.391