Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients

Two parallel randomized, placebo-controlled, double-blind clinical trials

Kenneth David Boffard, Bruno Riou, Brian Warren, Philip Iau Tsau Choong, Sandro Rizoli, Rolf Rossaint, Mads Axelsen, Yoram Kluger, Howard R. Champion, Charles Lucas, Errington Thompson, Steve Ross, Gregory Jurkovich, Mauricio Lynn, Lawrence Pitts, Martin A. Croce

Research output: Contribution to journalArticle

609 Citations (Scopus)

Abstract

Background: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma. Methodsd: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 μg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose. Results: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups. Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.

Original languageEnglish (US)
Pages (from-to)8-18
Number of pages11
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume59
Issue number1
DOIs
StatePublished - Jul 1 2005
Externally publishedYes

Fingerprint

Placebos
Clinical Trials
Hemorrhage
Wounds and Injuries
Erythrocyte Transfusion
Therapeutics
recombinant FVIIa
Erythrocytes
Safety
Cause of Death
Mortality
Population

Keywords

  • Blood transfusion
  • Blunt trauma
  • Coagulopathy
  • Hemorrhage
  • Massive transfusion
  • Penetrating trauma
  • Recombinant factor VIIa
  • Trauma

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

Cite this

Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients : Two parallel randomized, placebo-controlled, double-blind clinical trials. / Boffard, Kenneth David; Riou, Bruno; Warren, Brian; Choong, Philip Iau Tsau; Rizoli, Sandro; Rossaint, Rolf; Axelsen, Mads; Kluger, Yoram; Champion, Howard R.; Lucas, Charles; Thompson, Errington; Ross, Steve; Jurkovich, Gregory; Lynn, Mauricio; Pitts, Lawrence; Croce, Martin A.

In: Journal of Trauma - Injury, Infection and Critical Care, Vol. 59, No. 1, 01.07.2005, p. 8-18.

Research output: Contribution to journalArticle

Boffard, KD, Riou, B, Warren, B, Choong, PIT, Rizoli, S, Rossaint, R, Axelsen, M, Kluger, Y, Champion, HR, Lucas, C, Thompson, E, Ross, S, Jurkovich, G, Lynn, M, Pitts, L & Croce, MA 2005, 'Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: Two parallel randomized, placebo-controlled, double-blind clinical trials', Journal of Trauma - Injury, Infection and Critical Care, vol. 59, no. 1, pp. 8-18. https://doi.org/10.1097/01.TA.0000171453.37949.B7
Boffard, Kenneth David ; Riou, Bruno ; Warren, Brian ; Choong, Philip Iau Tsau ; Rizoli, Sandro ; Rossaint, Rolf ; Axelsen, Mads ; Kluger, Yoram ; Champion, Howard R. ; Lucas, Charles ; Thompson, Errington ; Ross, Steve ; Jurkovich, Gregory ; Lynn, Mauricio ; Pitts, Lawrence ; Croce, Martin A. / Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients : Two parallel randomized, placebo-controlled, double-blind clinical trials. In: Journal of Trauma - Injury, Infection and Critical Care. 2005 ; Vol. 59, No. 1. pp. 8-18.
@article{7c5988277a934bff8640bfcf5e535af0,
title = "Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: Two parallel randomized, placebo-controlled, double-blind clinical trials",
abstract = "Background: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma. Methodsd: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 μg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose. Results: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14{\%} vs. 33{\%} of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7{\%} vs. 19{\%}; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups. Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.",
keywords = "Blood transfusion, Blunt trauma, Coagulopathy, Hemorrhage, Massive transfusion, Penetrating trauma, Recombinant factor VIIa, Trauma",
author = "Boffard, {Kenneth David} and Bruno Riou and Brian Warren and Choong, {Philip Iau Tsau} and Sandro Rizoli and Rolf Rossaint and Mads Axelsen and Yoram Kluger and Champion, {Howard R.} and Charles Lucas and Errington Thompson and Steve Ross and Gregory Jurkovich and Mauricio Lynn and Lawrence Pitts and Croce, {Martin A.}",
year = "2005",
month = "7",
day = "1",
doi = "10.1097/01.TA.0000171453.37949.B7",
language = "English (US)",
volume = "59",
pages = "8--18",
journal = "Journal of Trauma and Acute Care Surgery",
issn = "2163-0755",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients

T2 - Two parallel randomized, placebo-controlled, double-blind clinical trials

AU - Boffard, Kenneth David

AU - Riou, Bruno

AU - Warren, Brian

AU - Choong, Philip Iau Tsau

AU - Rizoli, Sandro

AU - Rossaint, Rolf

AU - Axelsen, Mads

AU - Kluger, Yoram

AU - Champion, Howard R.

AU - Lucas, Charles

AU - Thompson, Errington

AU - Ross, Steve

AU - Jurkovich, Gregory

AU - Lynn, Mauricio

AU - Pitts, Lawrence

AU - Croce, Martin A.

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Background: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma. Methodsd: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 μg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose. Results: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups. Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.

AB - Background: Uncontrolled bleeding is a leading cause of death in trauma. Two randomized, placebo-controlled, double-blind trials (one in blunt trauma and one in penetrating trauma) were conducted simultaneously to evaluate the efficacy and safety of recombinant factor VIIa (rFVIIa) as adjunctive therapy for control of bleeding in patients with severe blunt or penetrating trauma. Methodsd: Severely bleeding trauma patients were randomized to rFVIIa (200, 100, and 100 μg/kg) or placebo in addition to standard treatment. The first dose followed transfusion of the eighth red blood cell (RBC) unit, with additional doses 1 and 3 hours later. The primary endpoint for bleeding control in patients alive at 48 hours was units of RBCs transfused within 48 hours of the first dose. Results: Among 301 patients randomized, 143 blunt trauma patients and 134 penetrating trauma patients were eligible for analysis. In blunt trauma, RBC transfusion was significantly reduced with rFVIIa relative to placebo (estimated reduction of 2.6 RBC units, p = 0.02), and the need for massive transfusion (>20 units of RBCs) was reduced (14% vs. 33% of patients; p = 0.03). In penetrating trauma, similar analyses showed trends toward rFVIIa reducing RBC transfusion (estimated reduction of 1.0 RBC units, p = 0.10) and massive transfusion (7% vs. 19%; p = 0.08). Trends toward a reduction in mortality and critical complications were observed. Adverse events including thromboembolic events were evenly distributed between treatment groups. Recombinant FVIIa resulted in a significant reduction in RBC transfusion in severe blunt trauma. Similar trends were observed in penetrating trauma. The safety of rFVIIa was established in these trauma populations within the investigated dose range.

KW - Blood transfusion

KW - Blunt trauma

KW - Coagulopathy

KW - Hemorrhage

KW - Massive transfusion

KW - Penetrating trauma

KW - Recombinant factor VIIa

KW - Trauma

UR - http://www.scopus.com/inward/record.url?scp=24644491444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24644491444&partnerID=8YFLogxK

U2 - 10.1097/01.TA.0000171453.37949.B7

DO - 10.1097/01.TA.0000171453.37949.B7

M3 - Article

VL - 59

SP - 8

EP - 18

JO - Journal of Trauma and Acute Care Surgery

JF - Journal of Trauma and Acute Care Surgery

SN - 2163-0755

IS - 1

ER -