Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage.
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].).
Mayer
Stephan A
SA
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, USA. sam14@columbia.edu
Brun
Nikolai C
NC
Begtrup
Kamilla
K
Broderick
Joseph
J
Davis
Stephen
S
Diringer
Michael N
MN
Skolnick
Brett E
BE
Steiner
Thorsten
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D004311:Double-Blind Method; D015942:Factor VIIa / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D015600:Glasgow Coma Scale; D006406:Hematoma / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure
D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa