In Summary, for those who got the Factor VII:

Benefits in NNT

  • 100% saw no benefit
  • None were helped (life saved)

Harms in NNT

  • 0% were harmed by thromboembolic events compared to placebo
  • None were harmed (thromboembolic events)

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Source: Logan AC, Yank V, Stafford RS. Off-label use of recombinant factor VIIa in U.S. Hospitals: analysis of hospital records. Ann Intern Med. 154(8): 516-522, April 2011.

Boffard KD, Riou B, Warren B, et al. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-controlled, double-blind clinical trials. J Trauma. 2005;59:8-15.

Nishijima DK, Zehtabchi S. The efficacy of recombinant activated factor VII in severe trauma. Ann Emerg Med. 2009 Nov;54(5):737-744.

Hauser CJ, Bofford K, Dutton R, et al. Results of the CONTROL trial: efficacy and safety of recombinant activated factor VII in the management of refractory traumatic hemorrhage. Journal of Trauma. 2010 Sep;69(3):489-500.

Efficacy Endpoints: Primary endpoints: Mortality; Secondary endpoints: Blood products needed, multiple morbidity events (i.e. ventilator days, ICU days, etc)

Harm Endpoints: Thromboembolic events

Narrative: Uncontrollable hemorrhage is a significant problem in severe trauma. Traumatic injury leads to a relative coagulopathy through a number of mechanisms. Recombinant activated factor VIIa (rFVIIa) was developed for the treatment of bleeding episodes in patients with hemophilia who acquire antibodies to factor VII, and the Food and Drug Administration has approved it for this indication. rFVIIa has been used off-label in a number of bleeding conditions including severe trauma.1

To date, the only existing data on rFVIIa in severe trauma is from the CONTROL trial, a prospective double-blind multicenter study4: Phase 2 RCT (277 subjects)2 and Phase 3 (573 subjects)3. Severe trauma in this study was defined as the need for transfusion of 4 or more units of packed RBCs within 4 hours of admission. The trial included both blunt and penetrating trauma but excluded isolated head injury, moribund patients, or those with injuries stabilized by standard hemostatic interventions.

There was no statistically significant difference in mortality at 48 hours or at 30 days between the two groups; the phase 3 trial was stopped early due to enrollment difficulties and analysis suggesting futility. There were slight decreases in transfusion products needed though given the small numbers the confidence intervals were wide and with significant overlap. Contrary to most other data there was no detectable increase in adverse thromboembolic events with rFVIIa.

Caveats: Based on this one trial rFVIIa has not been shown to decrease mortality. There may be a modest decrease in blood product transfusion but it is unclear if or how this would translate into clinical benefits.

An interesting point to note is that the authors found a much lower mortality in both study arms than expected (13% found versus 30% expected). They theorize that this may be due to improving trauma care and add that improved survival with the administration of any one agent is unlikely.

Author: Sebastian Siadecki, MD

Published/Updated: August 25, 2011

  1. The Title Bar

    The title bar is color-coded with our overall recommendation.

    • Green: Benefits outweigh risks.
    • Yellow: Unclear risk/benefit profile.
    • Red: Benefits do not outweigh risks.
    • Black: Obvious harms, no clear benefits.
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