Safety and Efficacy of Recombinant Activated Factor VII - Safety and Efficacy of Recombinant Activated Factor VII

Jul 01, 2009
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
Novo Nordisk A/S
Date Published:
01/01/2009
Date Updated:
07/01/2009
Original Posted Date:
07/01/2009
References

Description:

The goal of this trial was to evaluate treatment with recombinant activated factor VII (rFVIIa) compared with placebo among bleeding patients after cardiac surgery.

Hypothesis:

rFVIIa would be more effective in reducing serious adverse events.

Study Design

  • Randomized
  • Blinded
  • Parallel

Patients Screened: 2,619
Patients Enrolled: 172
Mean Follow Up: 30 days
Mean Patient Age: 63 years
Female: 29%

Patient Populations:

  • Patients with excessive bleeding from mediastinal drains after at least 30 minutes in the intensive care unit

Primary Endpoints:

  • Incidence of critical serious adverse events

Secondary Endpoints:

  • Rate of reoperation
  • Amount of blood loss
  • Transfusion of allogeneic blood

Drug/Procedures Used:

Bleeding patients after cardiac surgery were randomized to rFVIIa 40 µg/kg (n = 35), rFVIIa 80 µg/kg (n = 69), or placebo (n = 68).

Principal Findings:

Overall, 172 patients were randomized. There was no difference in baseline characteristics between the groups. In the rFVIIa 80 µg/kg group, the mean age was 63 years, 29% were women, body mass index was 25.5 kg/m2, 43% received antifibrinolytic therapy, and mean cardiopulmonary bypass was 115 minutes.

The incidence of critical serious adverse events was 12% with rFVIIa 80 µg/kg, 14% with rFVIIa 40 µg/kg, and 7% with placebo (n = 0.40).

Death occurred in 9%, 11%, and 6%, stroke in 3%, 6%, and 0%, myocardial infarction in 0%, 0%, and 2%, and pulmonary embolism in 0%, 0%, and 0%, respectively for rFVIIa 80 µg/kg, rFVIIa 40 µg/kg, and placebo.

Reoperation for bleeding occurred in 12%, 14%, and 25% (p = 0.04) and allogeneic blood transfusion volume was 500 ml, 640 ml, and 825 ml (p = 0.042), respectively for rFVIIa 80 µg/kg, rFVIIa 40 µg/kg, and placebo.

Interpretation:

Among patients who are bleeding after cardiac surgery, the use of rFVIIa was associated with a nonsignificant increase in critical serious adverse events. There were numerically more deaths and strokes in the rFVIIa groups, which is consistent with observational data. This therapy did reduce the need for reoperation due to bleeding and the volume of allogeneic blood transfusion.

The investigators of this study appropriately expressed caution about the use of this agent until larger clinical trials are reported. This also provides a reminder about the use of aprotinin during cardiac surgery, which was commonly employed to reduce bleeding. However, the BART trial revealed that aprotinin increased the risk for death.

References:

Gill R, Herbertson M, Vuylsteke A, et al. Safety and efficacy of recombinant activated factor VII: a randomized placebo-controlled trial in the setting of bleeding after cardiac surgery. Circulation 2009;120:21-7.

Keywords: Myocardial Infarction, Stroke, Pulmonary Embolism, Coronary Disease, Aprotinin, Blood Transfusion, Reoperation, Body Mass Index, Research Personnel, Recombinant Proteins, Factor VIIa, Cardiopulmonary Bypass, Cardiac Surgical Procedures, Hemorrhage


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