Clinical trial NCT02203968: Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST)
Official title: Fibrinogen in the Initial Resuscitation of Severe Trauma (FiiRST): a Randomized Feasibility Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Trauma
Injury
Bleeding
Haemorrhage
Coagulopathy
Keywords: Fibrinogen replacement
Trauma coagulopathy
Hypofibrinogenemia
Early trauma coagulopathy
Haemorrhage
Fibrinogen concentrate
Feasibility trial
Clinical trials
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
First posted: 2014-07-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 Alternately, many Europeans countries where cryoprecipitate has been withdrawn from the market due to safety concerns, use fibrinogen concentrate.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.


Eligibility criteria: Inclusion Criteria:

1. Injured trauma (penetrating or blunt) patients who are at risk of significant bleeding, defined as: i. Systolic blood pressure (SBP) ≤ 100mmHg at any time from the injury scene until 30min after hospital admission AND ii. Red blood cell transfusion has been ordered by the trauma team leader (or delegate)

Exclusion Criteria:

1. Patients in shock which the etiology is purely not related to bleeding:

   i. Cardiogenic (myocardial or valvular dysfunction); ii. Distributive (septic, anaphylactic, acute adrenal insufficiency and neurogenic) and iii. Obstructive (cardiac tamponade, tension pneumothorax and massive pulmonary emboli).
2. Severe head injury, defined as any of the following:

   i. Glasgow coma scale (GCS) of 3 due to severe traumatic brain injury (TBI); ii. TBI with clear indication of immediate neurosurgical intervention based on clinical findings (mechanism of trauma associated with focal signs such as anisocoria with fixed pupil) or on CT results (bleeding causing mass effect); iii. Unsalvageable head injury such as through-through gunshot wound to the head, open skull fracture with exposure/loss of brain tissue; as per the trauma team or neurosurgery initial clinical assessment or as per initial CT of the head findings;
3. Known complete or incomplete spinal cord injury;
4. Known hereditary or acquired coagulopathies unrelated to the trauma resuscitation (e.g. known hepatic dysfunction);
5. Use of anticoagulant medications such as warfarin, low-molecular weight heparin, and direct thrombin and factor Xa inhibitors;
6. Moribund with evidence of unsalvageable injuries and withdrawal of care, as per the trauma team;
7. Received blood products prior to admission;
8. Patients with estimated body weight under 50Kg;
9. Patients with known or suspected pregnancy;
10. Patients arriving more than 6hr after injury.

Primary outcomes:
measure: Feasibility
timeFrame: One year
Secondary outcomes:
measure: Other feasibility endpoints and physiologic endpoints
timeFrame: one year
Other outcomes:
measure: Clinical Parameters
timeFrame: one year
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre, University of Toronto
name: Barto Nascimento, MD MSc
role: PRINCIPAL_INVESTIGATOR
References: