Efficacy and Safety of Activated Recombinant Human Factor VII in Severely Injured Trauma Patients

Trauma Clinical Trial

Official title:

A Multi-centre, Randomised, Double-blind, Parallel Group, Placebo Controlled Trial to Evaluate the Efficacy and Safety of Activated Recombinant Factor VII (rFVIIa/NovoSeven®/ Niastase®) in the Treatment of Bleeding in Severely Injured Trauma Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01563523
• Other study ID #: F7TRAUMA-2159
• Status: Completed
• Phase: Phase 2
• First received: March 23, 2012
• Last updated: January 12, 2017
• Start date: March 2002
• Est. completion date: October 2003

Study information

• Verified date: January 2017
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Africa, Asia, Europe, Oceania and North America. The aim of this trial is to evaluate the efficacy of activated recombinant human factor VII given in conjunction with standard therapy in the treatment of massive bleeding in subjects with severe blunt and/or penetrating trauma injury.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 283
• Est. completion date: October 2003
• Est. primary completion date: October 2003
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 65 Years

Eligibility

Inclusion Criteria:

• Informed consent obtained from the subject and/or his/her legally authorised representative (LAR) before any trial-related activities

• Injury(ies) due to a blunt and or penetrating trauma

• Receipt of 6 units of PRBC within a 4 hour period following admittance to the trauma centre

• Receipt of 8 units of PRBC upon administration of trial drug

Exclusion Criteria:

• Prehospital cardiac arrest

• Cardiac arrest in the ER or OR

• Gunshot wound to the head

• Glasgow Coma Scale below 8

• Base deficit of above 15 mEq/l or severe acidosis

• Transfusion of 8 units or more of PRBC prior to arrival in trauma centre

Related Conditions & MeSH terms

• Acquired Bleeding Disorder
• Blood Coagulation Disorders
• Hemorrhage
• Hemostatic Disorders
• Trauma
• Wounds and Injuries

Intervention

Drug:
• activated recombinant human factor VII
Standard therapy in conjunction with three single doses of rFVIIa administered over a 3 hour period. Administered once the subject has received 8 units of PRBC
• placebo
Standard therapy in conjunction with three single doses of placebo administered over a 3 hour period. Administered once the subject has received 8 units of PRBC

Locations

Country	Name	City	State
Australia	Novo Nordisk Investigational Site	Perth
Austria	Novo Nordisk Investigational Site	Graz
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
France	Novo Nordisk Investigational Site	Paris
Germany	Novo Nordisk Investigational Site	Aachen
Israel	Novo Nordisk Investigational Site	Jerusalem
Singapore	Novo Nordisk Investigational Site	Singapore
South Africa	Novo Nordisk Investigational Site	Cape Town	Western Cape
United Kingdom	Novo Nordisk Investigational Site	Birmingham

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Australia,  Austria,  Canada,  France,  Germany,  Israel,  Singapore,  South Africa,  United Kingdom, 

References & Publications (9)

Boffard KD, Riou B, Warren B, Choong PI, Rizoli S, Rossaint R, Axelsen M, Kluger Y; NovoSeven Trauma Study Group.. Recombinant factor VIIa as adjunctive therapy for bleeding control in severely injured trauma patients: two parallel randomized, placebo-con — View Citation

Champion HR, Fingerhut A, Escobar MA, Weiskopf RB. The role of data and safety monitoring in acute trauma resuscitation research. J Am Coll Surg. 2007 Jan;204(1):73-83. — View Citation

Hsia CC, Chin-Yee IH, McAlister VC. Use of recombinant activated factor VII in patients without hemophilia: a meta-analysis of randomized control trials. Ann Surg. 2008 Jul;248(1):61-8. doi: 10.1097/SLA.0b013e318176c4ec. — View Citation

Klitgaard T, Tabanera y Palacios R, Boffard KD, Iau PT, Warren B, Rizoli S, Rossaint R, Kluger Y, Riou B; NovoSeven Trauma Study Group.. Pharmacokinetics of recombinant activated factor VII in trauma patients with severe bleeding. Crit Care. 2006;10(4):R1 — View Citation

Kluger Y, Riou B, Rossaint R, Rizoli SB, Boffard KD, Choong PI, Warren B, Tillinger M. Safety of rFVIIa in hemodynamically unstable polytrauma patients with traumatic brain injury: post hoc analysis of 30 patients from a prospective, randomized, placebo-c — View Citation

Levy JH, Fingerhut A, Brott T, Langbakke IH, Erhardtsen E, Porte RJ. Recombinant factor VIIa in patients with coagulopathy secondary to anticoagulant therapy, cirrhosis, or severe traumatic injury: review of safety profile. Transfusion. 2006 Jun;46(6):919 — View Citation

Morris S, Ridley S, Munro V, Christensen MC. Cost effectiveness of recombinant activated factor VII for the control of bleeding in patients with severe blunt trauma injuries in the United Kingdom. Anaesthesia. 2007 Jan;62(1):43-52. — View Citation

Rizoli SB, Boffard KD, Riou B, Warren B, Iau P, Kluger Y, Rossaint R, Tillinger M; NovoSeven Trauma Study Group.. Recombinant activated factor VII as an adjunctive therapy for bleeding control in severe trauma patients with coagulopathy: subgroup analysis — View Citation

Rossaint R, Christensen MC, Choong PI, Boffard KD, Riou B, Rizoli S, Kluger Y, Lefering R, Morris S; NovoSeven® Trauma Study Group.. Cost-Effectiveness of Recombinant Activated Factor VII as Adjunctive Therapy for Bleeding Control in Severely Injured Trau — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of PRBC (packed red blood cells) units (allogeneic/autologous) transfused
Secondary	Adverse Events
Secondary	Changes in coagulation related parameters: APTT (activated partial thromboplastin time), fibrinogen, D-dimers, anti thrombin-III, F1+2 (prothrombin fragment 1+2) and TAT (thrombin anti thrombin complex)

External Links

•   Clinical Trials at Novo Nordisk