Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

Stephan A Mayer; Nikolai C Brun; Kamilla Begtrup; Joseph Broderick; Stephen Davis; Michael N Diringer; Brett E Skolnick; Thorsten Steiner; FAST Trial Investigators; Helle Klingenberg Iversen

doi:10.1056/NEJMoa0707534

Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

Stephan A Mayer, Nikolai C Brun, Kamilla Begtrup, Joseph Broderick, Stephen Davis, Michael N Diringer, Brett E Skolnick, Thorsten Steiner, FAST Trial Investigators, Helle Klingenberg Iversen

Institut for Klinisk Medicin

886 Citationer (Scopus)

Abstract

BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes.

METHODS: We randomly assigned 841 patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or death according to the modified Rankin scale 90 days after the stroke.

RESULTS: Treatment with 80 microg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26% in the placebo group, as compared with 18% in the group receiving 20 microg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 microg (P<0.001). The growth in volume of intracerebral hemorrhage was reduced by 2.6 ml (95% confidence interval [CI], -0.3 to 5.5; P=0.08) in the group receiving 20 microg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 microg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in the placebo group, 26% in the group receiving 20 microg of rFVIIa per kilogram, and 29% in the group receiving 80 microg). The overall frequency of thromboembolic serious adverse events was similar in the three groups; however, arterial events were more frequent in the group receiving 80 microg of rFVIIa than in the placebo group (9% vs. 4%, P=0.04).

CONCLUSIONS: Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov].).

Originalsprog	Engelsk
Tidsskrift	New England Journal of Medicine
Vol/bind	358
Udgave nummer	20
Sider (fra-til)	2127-37
Antal sider	11
ISSN	0028-4793
DOI	https://doi.org/10.1056/NEJMoa0707534
Status	Udgivet - 15 maj 2008

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10.1056/NEJMoa0707534

Citationsformater

@article{44349fef56614db18838808fdd5677a4,

title = "Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage",

abstract = "BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes.METHODS: We randomly assigned 841 patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or death according to the modified Rankin scale 90 days after the stroke.RESULTS: Treatment with 80 microg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26% in the placebo group, as compared with 18% in the group receiving 20 microg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 microg (P<0.001). The growth in volume of intracerebral hemorrhage was reduced by 2.6 ml (95% confidence interval [CI], -0.3 to 5.5; P=0.08) in the group receiving 20 microg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 microg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in the placebo group, 26% in the group receiving 20 microg of rFVIIa per kilogram, and 29% in the group receiving 80 microg). The overall frequency of thromboembolic serious adverse events was similar in the three groups; however, arterial events were more frequent in the group receiving 80 microg of rFVIIa than in the placebo group (9% vs. 4%, P=0.04).CONCLUSIONS: Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov].).",

keywords = "Adult, Aged, Aged, 80 and over, Cerebral Hemorrhage, Double-Blind Method, Factor VIIa, Female, Glasgow Coma Scale, Hematoma, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Recombinant Proteins, Tomography, X-Ray Computed, Treatment Failure",

author = "Mayer, {Stephan A} and Brun, {Nikolai C} and Kamilla Begtrup and Joseph Broderick and Stephen Davis and Diringer, {Michael N} and Skolnick, {Brett E} and Thorsten Steiner and {FAST Trial Investigators} and Iversen, {Helle Klingenberg}",

year = "2008",

month = may,

day = "15",

doi = "10.1056/NEJMoa0707534",

language = "English",

volume = "358",

pages = "2127--37",

journal = "New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

number = "20",

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TY - JOUR

T1 - Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

AU - Mayer, Stephan A

AU - Brun, Nikolai C

AU - Begtrup, Kamilla

AU - Broderick, Joseph

AU - Davis, Stephen

AU - Diringer, Michael N

AU - Skolnick, Brett E

AU - Steiner, Thorsten

AU - FAST Trial Investigators

AU - Iversen, Helle Klingenberg

PY - 2008/5/15

Y1 - 2008/5/15

N2 - BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes.METHODS: We randomly assigned 841 patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or death according to the modified Rankin scale 90 days after the stroke.RESULTS: Treatment with 80 microg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26% in the placebo group, as compared with 18% in the group receiving 20 microg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 microg (P<0.001). The growth in volume of intracerebral hemorrhage was reduced by 2.6 ml (95% confidence interval [CI], -0.3 to 5.5; P=0.08) in the group receiving 20 microg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 microg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in the placebo group, 26% in the group receiving 20 microg of rFVIIa per kilogram, and 29% in the group receiving 80 microg). The overall frequency of thromboembolic serious adverse events was similar in the three groups; however, arterial events were more frequent in the group receiving 80 microg of rFVIIa than in the placebo group (9% vs. 4%, P=0.04).CONCLUSIONS: Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov].).

AB - BACKGROUND: Intracerebral hemorrhage is the least treatable form of stroke. We performed this phase 3 trial to confirm a previous study in which recombinant activated factor VII (rFVIIa) reduced growth of the hematoma and improved survival and functional outcomes.METHODS: We randomly assigned 841 patients with intracerebral hemorrhage to receive placebo (268 patients), 20 microg of rFVIIa per kilogram of body weight (276 patients), or 80 microg of rFVIIa per kilogram (297 patients) within 4 hours after the onset of stroke. The primary end point was poor outcome, defined as severe disability or death according to the modified Rankin scale 90 days after the stroke.RESULTS: Treatment with 80 microg of rFVIIa per kilogram resulted in a significant reduction in growth in volume of the hemorrhage. The mean estimated increase in volume of the intracerebral hemorrhage at 24 hours was 26% in the placebo group, as compared with 18% in the group receiving 20 microg of rFVIIa per kilogram (P=0.09) and 11% in the group receiving 80 microg (P<0.001). The growth in volume of intracerebral hemorrhage was reduced by 2.6 ml (95% confidence interval [CI], -0.3 to 5.5; P=0.08) in the group receiving 20 microg of rFVIIa per kilogram and by 3.8 ml (95% CI, 0.9 to 6.7; P=0.009) in the group receiving 80 microg, as compared with the placebo group. Despite this reduction in bleeding, there was no significant difference among the three groups in the proportion of patients with poor clinical outcome (24% in the placebo group, 26% in the group receiving 20 microg of rFVIIa per kilogram, and 29% in the group receiving 80 microg). The overall frequency of thromboembolic serious adverse events was similar in the three groups; however, arterial events were more frequent in the group receiving 80 microg of rFVIIa than in the placebo group (9% vs. 4%, P=0.04).CONCLUSIONS: Hemostatic therapy with rFVIIa reduced growth of the hematoma but did not improve survival or functional outcome after intracerebral hemorrhage. (ClinicalTrials.gov number, NCT00127283 [ClinicalTrials.gov].).

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Cerebral Hemorrhage

KW - Double-Blind Method

KW - Factor VIIa

KW - Female

KW - Glasgow Coma Scale

KW - Hematoma

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Middle Aged

KW - Recombinant Proteins

KW - Tomography, X-Ray Computed

KW - Treatment Failure

U2 - 10.1056/NEJMoa0707534

DO - 10.1056/NEJMoa0707534

M3 - Journal article

C2 - 18480205

SN - 0028-4793

VL - 358

SP - 2127

EP - 2137

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 20

ER -

Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

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