Information for Investigators

Investigating Fibrinogen in Severe Trauma

Night time shot of Gold Coast University Hospital - FEISTY Study

Associated with severe trauma is a unique complex and multifactorial coagulopathy of which the exact pathophysiological mechanisms have yet to be fully elucidated. Fibrinogen is widely accepted as a key blood clotting protein in maintaining haemostasis. It is the first factor to drop below reference values during bleeding and in trauma reached critically low levels earlier than any coagulation factor.

We hypothesise that fibrinogen replacement in severe traumatic haemorrhage can be achieved quicker with a more predictable dose response using Fibrinogen Concentrate compared to Cryoprecipitate.

The FEISTY study will investigate the use of Fibrinogen Concentrate against currently accepted standards of fibrinogen supplementation – cryoprecipitate using an accepted viscoelastic haemostatic assay (VHA) algorithm.

Recruitment is now complete for the FEISTY adult study

Specifics of the trial

Trial Aims

– To investigate the feasibility of fibrinogen replacement in severe traumatic haemorrhage utilising either FC or Cryoprecipitate

– Compare time to administration of fibrinogen replacement between FC and Cryoprecipitate

– To investigate the effects of fibrinogen replacement utilising either FC or Cryoprecipitate on fibrinogen levels during traumatic haemorrhage

– Investigating the feasibility of implementing the study protocol in a pilot multicentre study

– Use the data generated in the pilot study to inform on logistical considerations and guide planning of a large definitive multicentre study with patient centred outcome measures as primary endpoint

Trial Design

– Multi-centre (4 sites)

– Randomised controlled, un blinded, feasibility trial

Inclusion Criteria

1. Adults (>18yrs) affected by trauma AND

2. Judge to have significant haemorrhage OR

3. Predicted to require significant transfusion with ABC Score ≥ 2 or by treating clinician judgement

Exclusion Criteria

1. Injury incompatible with survival

2. Pregnancy

3. Known objection to blood products

4. Previous fibrinogen replacement this admission

5. Pre-trauma centre FC or Cryo replacement

6. Participation in a competing study

7. Patient has a known coagulation disorder i.e. Haemophilia, Von Willebrand disease

8. Randomisation unable to be performed within 6 hours of presentation to hospital

Intervention Diagram - FEISTY Study

Outcome Measures

Primary Outcome Measures

(1a) Time to administration of fibrinogen replacement from time of ROTEM analysis indicating fibrinogen supplementation is required
(1b) Feasibility of administering FC within 30 mins of clinical scenario and ROTEM analysis suggesting Fibrinogen replacement is required
(2) Effects on fibrinogen levels during traumatic haemorrhage as measured by Clauss Fibrinogen and FIBTEM analysis

Secondary Outcome Measures

(1) Transfusion requirements (in number of units or PRBC, FFP, FC, Cryoprecipitate, Platelets, PCC at 4, 6, 24, 48hrs);
(2) Duration of bleeding episode or time until surgical control and with no further requirement or coagulation factors;
(3) Duration of ICU and Hospital LOS;
(4) Duration of Mechanical ventilation;
(5) ROTEM, Multiplate, FBC, INR, APTT, FibC analysis at pre-specified time points – ED presentation OR recognition of significant haemorrhage, 10mins after intervention, as clinically indicated, after every 4 units PRBC, at ICU admission +6hrs, 12hrs and then daily for 7 days;
(6) Specific evaluation of EXTEM CT (clotting time) during active haemorrhage and in response to fibrinogen replacement;
(7) Adverse events – TACO/TRALU/Sepsis/MOF/ARF;
(8) thromboembolic complications;
(9) All-cause mortality at 4, 6, 24 hours and up to 90 days

Feasibility Outcome Measures

(1) Time to randomisation;
(2) FC or Cryoprecipitate wastage;
(3) Proportion of patients with blood sampling at all pre-specified time points;
(4) Number of missed patients (eligible but not enrolled);
(5) Randomisation errors;
(6) Protocol violations

Collaborators and Sponsors

This is an investigator initiated, designed and driven study coordinated from Gold Coast University Hospital.

Participating Sites

Gold Coast University Hospital
Gold Coast University Hospital
Royal Brisbane Womens Hospital
Royal Brisbane and Women's Hospital
Princess Alexandra Hospital
Princess Alexandra Hospital
Townsville Hospital
Townsville Hospital

We are fortunate to be supported by funding grants from

National Blood Authority Logo - FEISTY Study
Emergency Medicine Foundation logo - FEISTY Study
Gold Coast Health Logo - FEISTY Study

Our collaborators include

Australian Red Cross Blood Service Logo - FEISTY Study
University of Queensland Logo - FEISTY Study
Griffith University Logo - FEISTY Study

Research Grants from

tem Logo - FEISTY Study
Haemoview Diagnostics Logo - FEISTY Study
CSL Behring Logo - FEISTY Study

Industry support for the FEISTY study is limited to materials only with no input to the design and conduct of the study.