Fibrinogen Early In Severe Trauma StudY II

Study Overview
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Brief Summary
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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

Official Title
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Fibrinogen Early In Severe Trauma StudY II

Conditions
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Coagulopathy, Trauma, Haemorrhagic Shock

Intervention / Treatment
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* Drug: Fibrinogen Concentrate
* Other: Cryoprecipitate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A prospective phase III, multi-centre, randomised, controlled, two arm parallel, open label trial evaluating the effect of FC compared to standard care (Cryo) in severely injured bleeding adult trauma patients with major haemorrhage and hypofibrinogenemia.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibrinogen Concentrate (FC)<br>Fibrinogen Replacement using 3g Fibrinogen Concentrate as per: ROTEM FIBTEM A5 ≤ 10mm or TEG FF A10 ≤ 15mm or FibC ≤ 2g/L | Drug: Fibrinogen Concentrate<br>* 3g Fibrinogen Concentrate<br>* Other names: Riastap;|
| Active Comparator: Cryoprecipitate (Cryo)<br>Fibrinogen 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 | Other: Cryoprecipitate<br>* 10U WB or 4U Apheresis Cryoprecipitate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Days Alive and Out of Hospital at 90 Days | DAOH 90 | 90 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number RBC Units at 24 hours | Red Blood Cells | 24 hours | 
| All cause mortality at 90 days | Mortality at Day 90 | 90 days | 
| All cause mortality at 6 and 24 hours | Mortality at 6 and 24 hours | 24 hours | 
| Death from haemorrhage at 6 and 24 hours | Haemorrhage as cause of death at 6 and 24 hours | 24 hours | 
| Ventilator free days up to day 28 | VFD 28 days | 28 days | 
| Symptomatic thromboembolic events to 28 days | Venous and Arterial Thrombotic events | 28 days | 
| Quality of life at 3, 6 and 12 months | EQ5D-5L European Quality of Life 5 Dimensions 5 Levels Scored 0-100, where 0 = Worst QOL and 100 = Best QOL | 12 Months | 
| Health and disability at 3, 6 and 12 months | WHODAS 2.0 World Health Organisation Disability and Assessment Schedule 2.0 Scored 0-100, where 0 = No Disability and 100 = Full Disbility | 12 months | 
| Functional outcome (Patients with TBI) at 12 months | GOSE Glasgow Outcome Scale Extended Scored 1-8, where 1 = Death and 8 = Upper Good Recovery | 12 months | 
| Organ failure assessment | Denver MOF Score Denver Multiple Organ Failure Score Scored 0-12, where 0 = No Organ Failure and 12 = Severe MOF | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fibrinogen, Cryoprecipitate