BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality.Among patients who undergo computed tomograph y (CT) within three hours after the onset of intracerebral...BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality.Among patients who undergo computed tomograph y (CT) within three hours after the onset of intracerebral hemorrhage, one third have an increase in the volume of the hematoma related to subsequent bleeding. We sought to determine whether recombinant activated factor VII (rFVIIa) can red uce hematoma growth after intracerebral hemorrhage. METHODS: We randomly assigne d 399 patients with intracerebral hemorrhage diagnosed by CT within three hours after onset to receive placebo (96 patients) or 40 μg of rFVIIa per kilogram of body weight (108 patients), 80 μg per kilogram (92 patients), or 160 μg per k ilogram (103 patients) within one hour after the baseline scan. The primary outc ome measure was the percent change in the volume of the intracerebral hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Hematoma volu me increased more in the placebo group than in the rFVIIa groups. The mean incre ase was 29 percent in the placebo group, as compared with 16 percent, 14 percent , and 11 percent in the groups given 40 μg, 80 μg, and 160 μg of rFVIIa per k ilogram, respectively (P=0.01 for the comparison of the three rFVIIa groups with the placebo group). Growth in the volume of intracerebral hemorrhage was reduce d by 3.3 ml, 4.5 ml, and 5.8 ml in the three treatment groups, as compared with that in the placebo group (P=0.01). Sixty-nine percent of placebo-treated pati ents died or were severely disabled (as defined by a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49 percent, and 54 percent of the pati ents who were given 40, 80, and 160 μg of rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with the placebo group). Mortality at 90 days was 29 percent for patients who received placebo, as compared with 18 perce nt in the three rFVIIa groups combined (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral infarction, occurred in 7 percent of rFVII a-treated patients, as compared with 2 percent of those given placebo (P=0.12). CONCLUSIONS:Treatment with rFVIIa within four hours after the onset of intracer ebral hemorrhage limits the growth of the hematoma, reduces mortality, and impro ves functional outcomes at 90 days, despite a small increase in the frequency of thromboembolic adverse events.展开更多
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 VII (rFVIIa) promotes hemosta...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 VII (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 μ g/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- μ g/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.展开更多
文摘BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke and is associated with high mortality.Among patients who undergo computed tomograph y (CT) within three hours after the onset of intracerebral hemorrhage, one third have an increase in the volume of the hematoma related to subsequent bleeding. We sought to determine whether recombinant activated factor VII (rFVIIa) can red uce hematoma growth after intracerebral hemorrhage. METHODS: We randomly assigne d 399 patients with intracerebral hemorrhage diagnosed by CT within three hours after onset to receive placebo (96 patients) or 40 μg of rFVIIa per kilogram of body weight (108 patients), 80 μg per kilogram (92 patients), or 160 μg per k ilogram (103 patients) within one hour after the baseline scan. The primary outc ome measure was the percent change in the volume of the intracerebral hemorrhage at 24 hours. Clinical outcomes were assessed at 90 days. RESULTS: Hematoma volu me increased more in the placebo group than in the rFVIIa groups. The mean incre ase was 29 percent in the placebo group, as compared with 16 percent, 14 percent , and 11 percent in the groups given 40 μg, 80 μg, and 160 μg of rFVIIa per k ilogram, respectively (P=0.01 for the comparison of the three rFVIIa groups with the placebo group). Growth in the volume of intracerebral hemorrhage was reduce d by 3.3 ml, 4.5 ml, and 5.8 ml in the three treatment groups, as compared with that in the placebo group (P=0.01). Sixty-nine percent of placebo-treated pati ents died or were severely disabled (as defined by a modified Rankin Scale score of 4 to 6), as compared with 55 percent, 49 percent, and 54 percent of the pati ents who were given 40, 80, and 160 μg of rFVIIa, respectively (P=0.004 for the comparison of the three rFVIIa groups with the placebo group). Mortality at 90 days was 29 percent for patients who received placebo, as compared with 18 perce nt in the three rFVIIa groups combined (P=0.02). Serious thromboembolic adverse events, mainly myocardial or cerebral infarction, occurred in 7 percent of rFVII a-treated patients, as compared with 2 percent of those given placebo (P=0.12). CONCLUSIONS:Treatment with rFVIIa within four hours after the onset of intracer ebral hemorrhage limits the growth of the hematoma, reduces mortality, and impro ves functional outcomes at 90 days, despite a small increase in the frequency of thromboembolic adverse events.
文摘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 VII (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 μ g/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- μ g/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.
