Recombinant activated factor VII in spinal surgery: a multicenter, randomized, double-blind, placebo-controlled, dose-escalation trial.
METHODS
Randomized, placebo-controlled, double-blind, multicenter, Phase IIa study.


OBJECTIVE
To assess the safety and efficacy of recombinant-activated Factor VII (rFVIIa) in major spinal surgery.


BACKGROUND
Spinal fusion surgery can cause substantial blood loss and blood product transfusions. Recombinant FVIIa is approved for treatment of bleeding in patients with coagulation abnormalities and has been shown to reduce blood loss and transfusion requirements in surgery in patients with no underlying coagulopathy.


METHODS
Forty-nine patients undergoing fusion of 3 or more vertebral segments were randomized and treated on losing 10% of their estimated blood volume (with total expected surgical blood loss > or = 20%) and received 3 doses (2-hour intervals) of placebo (n = 13) or 30, 60, or 120 microg/kg rFVIIa (n = 12 per group). The primary endpoint was safety. A priori-defined efficacy endpoints included blood loss and transfusion requirements between placebo and each rFVIIa dose group, adjusted for surgery duration, number of segments fused, and estimated blood volume.


RESULTS
Serious adverse events did not occur at any greater frequency in any of the treatment groups. One patient (3 x 30 microg/kg rFVIIa) with advanced cerebrovascular disease (undiagnosed, trial exclusion criterion) died 6 days after surgery due to an ischemic stroke. Mean blood loss was as follows: 2270 mL for placebo; 1909, 1262, and 1868 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (differences not statistically significant). Mean adjusted surgical blood loss was as follows: 2536 mL for placebo; 1120, 400, and 823 mL for 3 x 30, 3 x 60, and 3 x 120 microg/kg rFVIIa, respectively (P < or = 0.001). Mean surgical transfusion volume was reduced by 27% to 50% with rFVIIa treatment (not significant). The mean adjusted surgical transfusion volume was reduced by 81% to 95% with rFVIIa treatment (P < or = 0.002).


CONCLUSIONS
No safety concerns were indicated for the use of rFVIIa in patients at all doses tested; rFVIIa reduced adjusted blood loss and adjusted transfusions during spinal surgery.
Sachs
Barton
B
Texas Back Institute Clinical Research Organization, Plano, TX, USA.
Delacy
Dawn
D
Green
Jeffrey
J
Graham
R Scott
RS
Ramsay
James
J
Kreisler
Nevin
N
Kruse
Peter
P
Khutoryansky
Naum
N
Hu
Serena S
SS
D000293:Adolescent; D000328:Adult; D000368:Aged; D016063:Blood Loss, Surgical / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005167:Factor VII / Q000008:administration & dosage* / Q000378:metabolism*; D015942:Factor VIIa; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D013122:Spinal Diseases / Q000188:drug therapy / Q000601:surgery; D013123:Spinal Fusion / Q000379:methods
D011994:Recombinant Proteins; D005167:Factor VII; C103587:recombinant FVIIa; D015942:Factor VIIa