Source: DGNews  |  Posted 2 years ago

By Evelyn Harvey

BRUSSELS, Belgium -- March 25, 2009 -- Red blood cell (RBC) and fresh frozen plasma (FFP) transfusions are significantly reduced by treatment with recombinant factor VIIa (rFVIIa), in patients suffering massive blood loss following trauma.

The study, presented here at the 29th International Symposium on Intensive Care and Emergency Medicine (ISICEM), also showed no effects on mortality or morbidity between treatment and control groups, but low overall mortality rates.

Interim results from the multicentre Assessment of rFVIIa in Controlling Bleeding in Patients With Severe Trauma Injuries (CONTROL) study were presented on March 25 by principal investigator Bertil Bouillon, MD, Merheim Hospital, Cologne, Germany.

Dr. Bouillon and colleagues set out to demonstrate a reduction in transfusions, mortality, and morbidity by early treatment of coagulopathy with rFVIIa.

A total of 573 patients with severe blunt (n = 481) or penetrating (n = 92) trauma who continued to haemorrhage after 4 to 8 RBC transfusions over 12 hours were randomised to rFVIIa treatment or placebo as an adjunct to standard care.

Patients randomised to treatment received a dose of intravenous rFVIIa 200 mcg/kg followed by 2 doses of rFVIIa 100 mcg/kg 1 and 3 hours after the first dose.

The study excluded those with major head trauma, moribund patients, or those who arrived in hospital over 4 hours post trauma.

There were no observed differences in baseline characteristics between both groups. However, blunt trauma patients had a higher injury severity score compared with penetrating trauma patients (32 vs 22-29).

Overall mortality for the trial was 11%, significantly below the expected 28%.

No significant differences were observed between blunt trauma patients receiving rFVIIa or placebo in mortality and morbidity 30 days post randomisation, multiple organ failure, severe adverse effects, massive transfusion (>=10 units), or in thromboembolic events.

However, the rFVIIa group required significantly fewer FFP (P = .0011), RBC (P = .04), and all allogeneic (P = .04) transfusions than the control patients.

Similar results were seen for penetrating trauma patients with the exception of a significant reduction in massive transfusion in the rFVIIa group (P = .04).

"Although rFVIIa works in reducing blood product transfusions, we have not shown that it helps in reducing mortality," concluded Dr. Bouillon, adding that further trials are needed to determine the potential role of rFVIIa in selected groups of patients. He also noted that rFVIIa use should be documented and recorded for future analysis.

The unexpectedly low mortality rate led to early termination of the trial because of lack of statistical power. "It is possible that the standardised guidelines for treatment we supplied to the trial centres had a beneficial effect on mortality and mortality," said Dr. Bouillon.

Funding for this study was provided by Novo Nordisk.

[Presentation title: The Place of rFVIIa: The CONTROL Study]