Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST)
Status:
Completed
Trial end date:
2015-12-01
Target enrollment:
Participant gender:
Summary
Trauma is the leading cause of death in people 44 years of age or younger. After major
trauma, such as following high-speed motor vehicle collision, bleeding coupled with clotting
defects is responsible for most of deaths in the first hours of hospital admission. Of note,
these bleeding-related deaths are potentially preventable. Accordingly, the initial
in-hospital management of severely injured patients focuses on stopping bleeding, replacing
blood loss and correcting clotting defects.
Recently, animal and human research demonstrated that one of the major clotting defects
following injury and bleeding is the drop in blood levels of fibrinogen (a clotting factor),
which is detected on hospital admission in severely injured patients. These low fibrinogen
levels are associated with increased blood transfusion and death. However, in North America,
the standard of care for replacing low fibrinogen requires the use of cryoprecipitate, which
is a frozen blood product with long preparation time, and similarly to other blood products,
carries the risk of viral transmission and transfusion complications. Alternately, many
Europeans countries where cryoprecipitate has been withdrawn from the market due to safety
concerns, use fibrinogen concentrate. Fibrinogen concentrate undergoes pathogen inactivation,
which is a process to eliminate the risk of transmitting viruses, bacteria and parasites, is
likely a safer and faster alternative to cryoprecipitate. In Canada, fibrinogen concentrate
is licensed for congenital low fibrinogen only.
Although preliminary data suggest that fibrinogen supplementation in trauma is associated
with reduced bleeding, blood transfusion, and death, the feasibility, safety and efficacy of
early fibrinogen replacement remains unknown. We proposed to conduct a feasibility randomized
trial to evaluate the use of early fibrinogen concentrate against placebo in injured patients
at our trauma centre.
A pilot trial is necessary to demonstrate the feasibility of rapidly preparing, delivering,
and infusing fibrinogen concentrate as an early therapy to prevent excessive bleeding in
trauma. This feasibility trial will provide preliminary safety and clinical outcome data to
inform the design of larger trials; which ultimately aims to prevent bleeding-related deaths
in the trauma population.