Key Point:

Recombinant factor VIIa significantly lowers the need for transfusions among blunt trauma patients who survive for at least 48 hours; whether it also reduces transfusion requirements among those with penetrating injuries remains unclear.

BRUSSELS—Recombinant factor VIIa (rFVIIa) is showing promise in severe trauma patients, according to the results of a randomized double-blind study. Findings were presented by Bruno Riou, MD, PhD, during the 24th International Symposium on Intensive Care and Emergency Medicine.[1]

The multicenter study included 301 trauma patients who were randomized to receive either rFVIIa or placebo (277 patients analyzed). Just over half of the patients (52%) had blunt injuries; the others had suffered penetrating trauma. The hemostatic agent was given in three doses: The first (200 µg/kg) was administered at study entry, and two additional doses (100 µg/kg each) were given within the next few hours. The study’s primary end point was the number of red blood cell units that needed to be transfused within 48 hours of the initial rFVIIa dose.

Among those who survived for at least 48 hours, rFVIIa significantly reduced the need for red blood cell transfusions in the group with blunt trauma. It also lowered the transfusion rate in those with penetrating trauma, although the difference was not statistically significant, noted Dr. Riou, who heads the Emergency Department at the Pitié-Salpêtrière University Hospital in Paris. Because 57 (21%) of the patients died within 48 hours, a significant reduction in the need for blood transfusions could not be demonstrated for the entire cohort. There also is the possibility that “if the drug delayed early death, … more blood could be administered,” said Dr. Riou.

The agent also lowered the number of patients who required massive transfusions (more than 20 units of red blood cells). The difference was significant in the group with blunt trauma (14% vs 33%) but not in those with penetrating trauma (7% vs 19%).

A secondary, composite end point was the percentage of patients who died or developed ARDS or multiorgan failure within 30 days. Among patients with blunt trauma, rFVIIa administration produced a striking decrease in this secondary end point: Only 29% of the patients given the hemostatic agent, compared with 43% of the placebo cohort, experienced one of these complications. Among the patients with penetrating trauma, however, much less of a difference was seen (30% vs 34%, respectively). Thirty-day survival was not considered a secondary end point because the study was not powered to provide an adequate comparison of that outcome.

Adverse events occurred with similar frequency among the rFVIIa recipients and the placebo cohort, an important consideration in patients who are at high risk for thromboembolic events, he noted. In both groups, however, adverse event rates were higher in the patients with blunt trauma than in those with penetrating injuries.

Dr. Riou concluded, “rFVIIa is a new and important therapeutic, and it does add to our treatments for coagulopathy in trauma patients. So, it can be used as a rescue drug, and it does have a high safety profile. But we still need further clinical studies to demonstrate an overt clinical impact of this drug on morbidity and mortality.”

—Patrice Olsen

Reference
1. Boffard K, Riou B, Warren P, et al, for the 31 international trial centers. Recombinant factor VIIa (Novoseven®) as adjunctive therapy to hemostasis in trauma. Presented at: 24th International Symposium on Intensive Care and Emergency Medicine; April 1, 2004; Brussels, Belgium.

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