Recombinant Factor VIIa as Adjunctive Therapy for Bleeding Control in Severely Injured Trauma Patients: Two Parallel Randomized, Placebo-Controlled, Double-Blind Clinical Trials

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Recombinant Factor VIIa as Adjunctive Therapy for
Bleeding Control in Severely Injured Trauma
Patients Two Parallel Randomized,
Placebo-Controlled, Double-Blind Clinical Trials

• Bofford KD, Riou B, Warren B, et al.
• J Trauma 2005598-18.

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Background

• Coagulopathy is a major contributing factor to
  bleeding related mortality in trauma.
• Coagulopathy in association with metabolic
  acidosis and hypothermia referred to as the
  Lethal Triad.

Boffard KD et al. J Trauma 2005598-18.
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Purpose

• Evaluate the efficacy and safety of rFVIIa as
  adjunctive therapy for control of bleeding in
  patients with severe blunt or penetrating trauma.

Boffard KD et al. J Trauma 2005598-18.
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Methods

• Blunt or penetrating trauma, 32 centers
• Inclusion
• Severely traumatized
• 6 units PRBC within 4 hours of admission
• 16 to lt 65 years
• Exclusion
• Cardiac arrest, GSW head, GCS lt 8 unless NL CT,
  BD gt 15, pH lt 7, 8 or more units PRBC prior to
  arrival to trauma center, injury 12 hours prior
  to randomization

Boffard KD et al. J Trauma 2005598-18.
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Methods

• Two parallel trials
• Blunt trauma and penetrating trauma
• Intervention
• Randomization to rFVIIa or PL
• Dose 200mcg, 100mcg, 100mcg at 0,1,3 hours,
  respectively, administered after the 8th unit
  PRBC
• Monitoring
• Transfusion and infusion requirements 48 h after
  rFVIIa
• Blood samples to evaluate changes in coagulation
  and blood biochemistry parameters

Boffard KD et al. J Trauma 2005598-18.
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End Points

• Primary end point
• RBC units 48 hours after first rFVIIa dose.
• Secondary end points
• Other transfusion products, mortality, days on
  ventilator, ICU LOS.
• Adverse events, coagulation-related lab variables
• Composite of death and critical complications
• MOF and ARDS

Boffard KD et al. J Trauma 2005598-18.
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Results- RBC Transfusions

• Estimated
• PL
  rFVIIa RBC reduction p
• N Median
  N Median 90 CI
• Blunt ( of Units) ( of Units) ( of Units)
• Alive 48 h 59 7.5 (0-35) 52 7.0(0-29)
  2.60.74.6 0.02
• All patients 72 7.2 (0-35) 64 7.8(0-48)
  2.00.04.6 0.07
• Penetrating
• Alive 48 h 52 4.2 (0-41) 57
  3.9(0-30) 1.00.02.6 0.10
• All patients 61 4.8 (0-41)
  69 4.0(0-37) 0.2-0.92.4 0.24

Boffard KD et al. J Trauma 2005598-18.
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Results- Need for Massive Transfusion
P0.03
P0.08
Boffard KD et al. J Trauma 2005598-18.
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Results- Mortality

• Blunt Trauma Penetrating Trauma
• PL (n74) rFVIIa (n69) p PL (n64)
  rFVIIa (n70) p
• Mortality
• 48 h M 13(18) 13(19) 1.00
  10(16) 12(17) 1.00
• 30 d M 22(30) 17(25) 0.58
  18(28) 17(24) 0.69

Boffard KD et al. J Trauma 2005598-18.
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Results- Clinical Outcomes

• Blunt Trauma Penetrating Trauma
• PL (n74) rFVIIa (n69) p PL (n64)
  rFVIIa (n70) p
• 30 day complication
• ARDS 12(16) 3(4) 0.03
  5(8) 4(6) 0.74
• MOF 9(12) 5(7) 0.41
  7(11) 2(3) 0.09
• Mortality, ARDS,
• or MOF 31(42) 20(29) 0.16
  22(34) 20(29) 0.57
• Vent free(d) 13 (0-29) 17(0-29) 0.43
  20(0-29) 25(0-29) 0.21
• ICU free(d) 8 (0-29) 12(0-29) 0.31
  18(0-29) 23(0-29) 0.34

Boffard KD et al. J Trauma 2005598-18.
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Results- Adverse Events

• Blunt Trauma Penetrating Trauma
• PL (n74) rFVIIa (n69) PL (n64)
  rFVIIa (n70)
• Serious adverse events
• Patients 49(66) 44(64) 36(56)
  36(51)
• No. events 109 91
  76 57
• Thrombotic adverse events
• Patients 3(4) 2(3) 3(5)
  4(6)
• No. events 3 2 3 4

Boffard KD et al. J Trauma 2005598-18.
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Conclusions

• rFVIIa significantly improved bleeding control in
  blunt trauma
• Decrease RBC transfusions
• Decrease in number of patients requiring massive
  transfusion
• Similar trend in patients with penetrating trauma
• Adverse events were not increased with rFVIIa

Boffard KD et al. J Trauma 2005598-18.