Fibrinogen Early In Severe Trauma StudY II

Overview

Annually over 7000 Australians are treated for severe trauma. Haemorrhage secondary to severe trauma is a major cause of potentially preventable death and poor outcomes in Australian adults. Severe trauma may trigger changes in blood clotting mechanisms and factor levels leading to inhibition of clot formation and reduced clot strength. This results in the inability of the severely injured trauma patient to form adequate clots to help stop bleeding. There is good evidence to suggest the loss of clotting factors during haemorrhage is associated with worse outcomes and it is thought the early replacement of these factors may reduce bleeding and improve patient outcomes. Fibrinogen is a key clotting factor that helps bind clots together and early fibrinogen replacement may improve outcomes. Currently fibrinogen is replaced using cryoprecipitate, a blood product made from blood donated by healthy donors which is a precious resource. It can take a significant amount of time to administer as it is frozen and stored in the blood bank. Timely administration of cryoprecipitate is difficult as it requires thawing prior to transfusion. The large doses of cryoprecipitate used in traumatic haemorrhage can put strain on local blood banks in supplying requested units in a timely manner. Additionally, the widely dispersed population of Australia introduces logistic challenges to the maintenance of adequate cryoprecipitate stocks to individual hospital blood banks, especially in remote regions. However, cryoprecipitate contains a number of other coagulation factors (not just fibrinogen) that may be instrumental in clot formation and resistance to fibrinolysis. Fibrinogen concentrate is an alternative product used to assist in blood clotting. It is a dry powder form of fibrinogen and can be reconstituted at the bedside and given quickly. The use of a fibrinogen factor concentrate with a long shelf life that is easy to use has significant implications for both large urban metropolitan areas and remote isolated communities. The timing and mode of fibrinogen replacement in traumatic haemorrhage has implications for patient outcomes, blood product availability, costs and the national blood supply. Despite the importance of fibrinogen replacement in traumatic haemorrhage, there have been no clinical trials powered for clinical outcomes directly comparing fibrinogen concentrate and cryoprecipitate. FEISTY II will evaluate the efficacy, safety and cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate in trauma patients with major haemorrhage. FEISTY II is a phase III randomised trial which will enrol 850 patients from Australian and New Zealand major trauma centres, with a primary patient outcome of days alive out of hospital at day 90 after injury. Severely injured trauma patients who require blood transfusion and have evidence of low fibrinogen levels will be randomised to receive either fibrinogen concentrate or standard care with cryoprecipitate

Interventions

• Drug Fibrinogen Concentrate
  3g Fibrinogen Concentrate
• Other Cryoprecipitate
  10U WB or 4U Apheresis Cryoprecipitate

Primary outcome measures

• Days Alive and Out of Hospital at 90 Days [Time frame: 90 Days]

Secondary outcome measures (10)

• Number RBC Units at 24 hours [Time frame: 24 hours]
• All cause mortality at 90 days [Time frame: 90 days]
• All cause mortality at 6 and 24 hours [Time frame: 24 hours]
• Death from haemorrhage at 6 and 24 hours [Time frame: 24 hours]
• Ventilator free days up to day 28 [Time frame: 28 days]
• Symptomatic thromboembolic events to 28 days [Time frame: 28 days]
• Quality of life at 3, 6 and 12 months [Time frame: 12 Months]
• Health and disability at 3, 6 and 12 months [Time frame: 12 months]
• Functional outcome (Patients with TBI) at 12 months [Time frame: 12 months]
• Organ failure assessment [Time frame: 28 days]

Eligibility criteria

Inclusion criteria

• Adult affected by trauma (≥18yrs)
• Judged to have active haemorrhage by treating clinician
• Activation of local MHP and/or Transfusion of Emergency Blood Products
• FIBTEM A5 ≤ 10mm or TEG FF A5 ≤ 15mm or FibC ≤ 2 g/l

Exclusion criteria

• Injury judged incompatible with survival
• Randomisation unable to occur within 6 hours of presentation to hospital
• Known pregnancy
• Known genetic or drug induced coagulation disorder
• Known objection to blood products
• Dedicated prior fibrinogen replacement
• Participation in a competing study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Australia · 20 centers

• John Hunter Hospital — Newcastle
• St Vincent's Hospital — Sydney
• Royal Prince Alfred Hospital — Sydney
• Royal North Shore Hospital — Sydney
• Westmead Hospital — Sydney
• Liverpool Hospital — Sydney
• Royal Darwin Hospital — Darwin
• Royal Brisbane and Women's Hospital — Brisbane
• … and 12 more centers

New Zealand · 4 centers

• Aukland City Hospital — Auckland
• Middlemore Hospital — Auckland
• Waikato Hospital — Hamilton
• Wellington Hospital — Wellington

Publications

• Fatovich DM, Carey S, Iliff J, Jowitt T, Weber DG, Vance JS. Integrating Research Practice Into Resuscitation Simulation Training Improves Recruitment Into Complex Clinical Trials. Emerg Med Australas. 2025 Jun;37(3):e70064. doi: 10.1111/1742-6723.70064. PMID 40420619

Identifiers

NCT: NCT05449834 · ANZIC-RC/ZM001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗