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Fibrinogen Early In Severe Trauma StudY II

Phase 3
Recruiting
Conditions
Trauma
Haemorrhagic Shock
Coagulopathy
Interventions
Other: Cryoprecipitate
Registration Number
NCT05449834
Lead Sponsor
Australian and New Zealand Intensive Care Research Centre
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
850
Inclusion Criteria
  1. Adult affected by trauma (≥18yrs)
  2. Judged to have active haemorrhage by treating clinician
  3. Activation of local MHP and/or Transfusion of Emergency Blood Products
  4. FIBTEM A5 ≤ 10mm or TEG FF A5 ≤ 15mm or FibC ≤ 2 g/l
Exclusion Criteria
  1. Injury judged incompatible with survival
  2. Randomisation unable to occur within 6 hours of presentation to hospital
  3. Known pregnancy
  4. Known genetic or drug induced coagulation disorder
  5. Known objection to blood products
  6. Dedicated prior fibrinogen replacement
  7. Participation in a competing study

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Fibrinogen Concentrate (FC)Fibrinogen ConcentrateFibrinogen Replacement using 3g Fibrinogen Concentrate as per: ROTEM FIBTEM A5 ≤ 10mm or TEG FF A10 ≤ 15mm or FibC ≤ 2g/L
Cryoprecipitate (Cryo)CryoprecipitateFibrinogen Replacement using 10 Units WB or 4U Apheresis Cryo (Australia) as per: ROTEM FIBTEM A5 ≤ 10mm or TEG FF A10 ≤ 15mm or FibC ≤ 2g/L
Primary Outcome Measures
NameTimeMethod
Days Alive and Out of Hospital at 90 Days90 Days

DAOH 90

Secondary Outcome Measures
NameTimeMethod
All cause mortality at 6 and 24 hours24 hours

Mortality at 6 and 24 hours

Ventilator free days up to day 2828 days

VFD 28 days

Symptomatic thromboembolic events to 28 days28 days

Venous and Arterial Thrombotic events

Quality of life at 3, 6 and 12 months12 Months

EQ5D-5L European Quality of Life 5 Dimensions 5 Levels Scored 0-100, where 0 = Worst QOL and 100 = Best QOL

Death from haemorrhage at 6 and 24 hours24 hours

Haemorrhage as cause of death at 6 and 24 hours

All cause mortality at 90 days90 days

Mortality at Day 90

Number RBC Units at 24 hours24 hours

Red Blood Cells

Health and disability at 3, 6 and 12 months12 months

WHODAS 2.0 World Health Organisation Disability and Assessment Schedule 2.0 Scored 0-100, where 0 = No Disability and 100 = Full Disbility

Functional outcome (Patients with TBI) at 12 months12 months

GOSE Glasgow Outcome Scale Extended Scored 1-8, where 1 = Death and 8 = Upper Good Recovery

Organ failure assessment28 days

Denver MOF Score Denver Multiple Organ Failure Score Scored 0-12, where 0 = No Organ Failure and 12 = Severe MOF

Trial Locations

Locations (2)

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

Gold Coast University Hospital

🇦🇺

Gold Coast, Queensland, Australia

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