A randomised, placebo-controlled, double-blind study to investigate the efficacy and safety of rFVIIa as adjunctive therapy for control of bleeding in patients with severe blunt trauma: a re-analysis following the exclusion of early (< 48 hours) deaths

Methods

Severely bleeding patients with blunt trauma were randomised to rFVIIa (200 + 100 + 100 μg/kg) or placebo as an adjunct to conventional treatment. Patients who had incurred both blunt and penetrating trauma were included in this study. First trial product injection followed the eighth RBC unit, with additional injections 1 hour and 3 hours later. The new efficacy analyses were performed on the patients surviving 48 hours or more after first administration of the trial product.

Results

Of 153 blunt trauma patients randomised, 117 were eligible for the primary efficacy analysis (10 patients were excluded because they did not receive the trial product due to death or arrest of bleeding before transfusion of the eighth unit of RBC, and 26 patients were excluded due to death within the 48-hour period). Total RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 total RBC units; 90% confidence interval: [0.7; 4.6]; P = 0.02) (results previously presented). The need for massive transfusion (> 20 RBC units, inclusive of the eight predose units administered pre trial product) was significantly reduced: 8/56 patients (14%) with rFVIIa versus 20/61 patients (33%) with placebo (P = 0.03), along with significant reductions in 48-hour requirements for FFP and platelets. The improved haemostasis was accompanied by a significant decrease in ARDS (3/56 [5%] of rFVIIa-treated vs 11/61 [18%] of placebo-treated patients [P = 0.047]) as well as a significant decrease in the risk of developing organ failure (either MOF or ARDS: 5/56 [9%] of rFVIIa-treated vs 15/61 [25%] of placebo-treated patients [P = 0.047]).

Conclusions

Recombinant FVIIa improved clinical outcome (risk of developing single or multiple organ failure, especially ARDS) in severely bleeding blunt trauma patients. No safety issues were identified.