Table 25General characteristics of comparative studies of off-label rFVIIa use for massive bleeding due to body trauma

ArticleStudy DesignStudy Setting and Time PeriodSample Size and Dose, μg/kgPopulation CharacteristicsOutcomes Evaluated
Mean Age (SD) [Range]Inclusion/Exclusion CriteriaDirectIndirect
Boffard 200596RCT

Treatment
32 centers

Australia, Canada, France, Germany, Israel, Singapore, South Africa and UK

3/2002–9/2003
All Rx: 139 -Blunt: 69 -Pen: 70

Usual care: 138 -Blunt: 74 -Pen: 64

Dose: 200 ug/kg after transfusion of eighth unit RBCs, followed by two 100 ug/kg doses at 1 and 3 hrs
Rx: Blunt: 33 (13) Pen: 29 (10)

Usual care: Blunt: 35 (13) Pen: 32 (10)
Inclusion: -severe trauma (i.e., 6 units of RBCs transfused within 4 hrs of admission) -between 16 and 65 years old

Exclusion:
-cardiac arrest before trial drug administration
-gunshot would to head
-GCS<8
-base deficit of 15 mEq/L or pH<7.0
-transfusion of 8 units or more RBCs before arrival at trauma center
-injury sustained >12 hrs before randomization
Mortality

Adverse events including TE events
Transfusion requirements (e.g. RBCs, FFP)

Hospital and ICU length of stay
Rizoli 200697bRetrospective comparative

Treatment
1 center

University of Toronto Health Sciences Centre, Toronto, Canada

1/2000–1/2005
All Rx: 38

Ucare: 204

Dose of rFVIIa is not reported
Rx: 36.8 [30.6–43.1]CI

Usual care: 41.1 [38.1–44.1]CI
Inclusion:
-traumatic hemorrhage
-8 or more units RBCs during first 12 hrs of hospitalization

Controls: Patients who met above inclusion criteria, but did not receive rFVIIa.
MortalityTransfusion requirements (e.g. RBCs, FFP)
Spinella 200898bRetrospective comparative

Treatment
Combat support hospitals in Iraq. Data from Joint Theatre Trauma Registry (JTTR)

12/2003–10/2005
All Rx: 49

Usual care: 75

Dose: Institutional guidelines suggested 120 ug/kg
Age not reportedInclusion:
-severe trauma (i.e. ISS>15)
-massive transfusion (i.e. transfusion of 10 units or more RBCs in 24 hrs)

Controls: Patients who met above inclusion criteria, but did not receive rFVIIa.
Mortality

Adverse events including TE events
Transfusion requirements (e.g. RBCs, FFP)
Fox 200999Retrospective comparative

Treatment
Combat support hospitals in Iraq. Data from Joint Theatre Trauma Registry (JTTR)

4/2006–8/2007
All Rx: 41

Usual care: 12

Dose: “typically” 90–120
Rx: 27.5 (9.4)

Usual care: 24 (10)
Inclusion:
-life-threatening hemorrhage (requiring > 4U PRBCs) from penetrating trauma that caused vascular injury which required repair
-received damage control resuscitation (minimal crystalloid use, use of whole blood or high ratio of plasma to RBCs (<1:1.4), and liberal replacement of platelets and cryoprecipitate

Exclusion: NR
Mortality

Adverse events including TE events
Transfusion requirements††
Dutton 2004100Retrospective comparative

Treatment
1 University hospital

USA

6/2001–12/2003
All Rx: 81

Usual care: 32- 449^

Dose: 100 for hemorrhagic shock; 50 for congenital or pharmacologic coagulopathy
Rx: 41 (21)

Usual care: NR
Inclusion:
-Receipt of at least 10 units PRBCs, 8 units FFP, and 1 pheresis unit platelets (the equivalent of 1 blood volume transfusion in components), with ongoing hemorrhage and evidence of coagulopathy (abnormal PT and PTT)
-Patient viability for meaningful longterm survivial as determined by institutional gatekeeper Exclusion:
-Lack of patient viability
Mortality

Adverse events including TE events
Transfusion

requirements†† Hospital LOS
Harrison 2005101Retrospective comparative

Treatment
1 Hospital

USA

2/2003–12/2003
All Rx: 29

Usual care: 72

Dose: 60
Rx: 41 (21)

Usual care: 42 (22)
Inclusion:
-Inclusion in prospectively collected trauma registry database Exclusion:
-No historical matched control could be identified
-Isolated closed head injury without hemorrhage
-Jehovah’s witness patient who declined all transfusions
Mortality

Venous TE events
Transfusion requirements ††

Hospital and ICU LOS

These studies did not meet inclusion criteria for detailed review in the comparative effectiveness analyses due to being poor quality (Table 14), but are included in the qualitative sensitivity discussions for this indication (in the section above, “Consideration of poor quality comparative observational studies”) and in the overall harms analyses near the end of this report.

CI

95% confidence interval;

U

Median; Pen=penetrating; SD=standard deviation; Rx=treatment group(s); TE=thromboembolic; RBCs=red blood cells; FFP=fresh frozen plasma; ISS=injury severity scale; ICU=intensive care unit

††

Examples of transfusion requirements were red blood cells and fresh frozen plasma

a

Nascimento et al.181 was used instead of Rizoli et al.97 in the harms analysis of thromboembolic events. Nascimento et al. is a continuation of Rizoli et al. with more patients.

b

Perkins 2007182 was used instead of Spinella 200898 in the harms analysis of mortality and TE events. Perkins 2007 is an overlapping non-comparative study with more patients.

^

Dutton 2004100 has multiple control groups. The range of sample sizes is presented.

From: Results

Cover of Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care
Comparative Effectiveness of In-Hospital Use of Recombinant Factor VIIa for Off-Label Indications vs. Usual Care [Internet].
Comparative Effectiveness Reviews, No. 21.
Yank V, Tuohy CV, Logan AC, et al.

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