Recombinant factor VIIA in traumatic intracerebral hemorrhage: results of a dose-escalation clinical trial.
OBJECTIVE
Intracerebral hemorrhages, whether spontaneous or traumatic (tICH), often expand, and an association has been described between hemorrhage expansion and worse clinical outcomes. Recombinant factor VIIa (rFVIIa) is a hemostatic agent that has been shown to limit hemorrhage expansion and which, therefore, could potentially reduce morbidity and mortality in tICH. This first prospective, randomized, placebo-controlled, dose-escalation study evaluated the safety and preliminary effectiveness of rFVIIa to limit tICH progression.


METHODS
Patients were enrolled if they had tICH lesions of at least 2 ml on a baseline computed tomographic scan obtained within 6 hours of injury. rFVIIa or placebo was administered within 2.5 hours of the baseline computed tomographic scan but no later than 7 hours after injury. Computed tomographic scans were repeated at 24 and 72 hours. Five escalating dose tiers were evaluated (40, 80, 120, 160, and 200 microg/kg rFVIIa). Clinical evaluations and adverse events were recorded until Day 15.


RESULTS
No significant differences were detected in mortality rate or number and type of adverse events among treatment groups. Asymptomatic deep vein thrombosis, detected on routinely performed ultrasound at Day 3, was observed more frequently in the combined rFVIIa treatment group (placebo, 3%; rFVIIa, 8%; not significant). A nonsignificant trend for rFVIIa dose-response to limit tICH volume increase was observed (placebo, 21.0 ml; rFVIIa, 10.1 ml).


CONCLUSIONS
In this first prospective study of rFVIIa in tICH, there appeared to be less hematoma progression in rFVIIa-treated patients (80-200 microg/kg) compared with that seen in placebo treated patients. The potential significance of this biological effect on clinical outcomes and the significance of the somewhat higher incidence of ultrasound-detected deep vein thromboses in the rFVIIa-treated group need to be examined in a larger prospective randomized clinical trial.
Narayan
Raj K
RK
Department of Neurosurgery, University of Cincinnati, Cincinnati, Ohio, USA.
Maas
Andrew I R
AI
Marshall
Lawrence F
LF
Servadei
Franco
F
Skolnick
Brett E
BE
Tillinger
Michael N
MN
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020202:Cerebral Hemorrhage, Traumatic / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015942:Factor VIIa / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D038622:Internationality; D020767:Intracranial Thrombosis / Q000139:chemically induced* / Q000175:diagnosis; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D015990:Placebo Effect; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
D011994:Recombinant Proteins; C103587:recombinant FVIIa; D015942:Factor VIIa