Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials.
BACKGROUND
Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma.


METHODS
Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 microg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose.


RESULTS
Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups.


CONCLUSIONS
Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.
Boffard
Kenneth David
KD
Department of Surgery, Johannesburg Hospital, University of the Witwatersrand, South Africa. kdboffard@pixie.co.za
Riou
Bruno
B
Warren
Brian
B
Choong
Philip Iau Tsau
PI
Rizoli
Sandro
S
Rossaint
Rolf
R
Axelsen
Mads
M
Kluger
Yoram
Y
D000328:Adult; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D017707:Erythrocyte Transfusion / Q000706:statistics & numerical data; D015942:Factor VIIa / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000209:etiology / Q000517:prevention & control*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D008297:Male; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D014947:Wounds and Injuries / Q000150:complications*
D015942:Factor VIIa