Fibrinogen Early In Severe Trauma studY (FEISTY)

Fibrinogen Concentrate vs Cryoprecipitate in Traumatic Haemorrhage: A Pilot Randomised Controlled Trial

• Haemorrhage in severe trauma is a significant cause of mortality and is potentially the most preventable cause of death in trauma patients
• Trauma Induced Coagulopathy (TIC) is a complex coagulopathy associated with severe trauma
• Hypo/dysfibrinogenaemia plays an important role in TIC
• Early replacement of fibrinogen may improve outcomes
• Fibrinogen replacement is potentially inadequate in standard fixed ratio Major Haemorrhage Protocols (MHP) utilising Plasma and/or Cryoprecipitate
• The majority of centres utilise cryoprecipitate for additional fibrinogen supplementation as part of a MHP
• Cryoprecipitate administration is often delayed (between 60 - 120 minutes) in a fixed ratio MHP
• It is clear early intervention in severe traumatic haemorrhage is associated with improved outcomes - CRASH 2 and PROPPR studies
• Increasing interest in the use of Fibrinogen Concentrate (FC) in severe bleeding but not supported by high level evidence
• Benefits of FC - viral inactivation, known dose, easily reconstituted, can be administered quickly in high dose and stored at room temperature in the trauma resuscitation bay
• No previous studies comparing FC and Cryoprecipitate in bleeding trauma patients
• Fibrinogen supplementation will be guided by an accepted ROTEM targeted treatment algorithm
• It will be a pilot, multi-centre randomised controlled trial comparing FC to Cryoprecipitate (current standard practise in fibrinogen supplementation)
• Hypothesis: Fibrinogen replacement in severe traumatic haemorrhage can be achieved quicker with a more predictable dose response using Fibrinogen Concentrate compared to Cryoprecipitate
• It is imperative that robust and clinically relevant trials are performed to investigate fibrinogen supplementation in trauma before widespread adoption makes performing such studies unfeasible

Study Overview

• Status: Completed
• Conditions: Trauma; Coagulopathy; Haemorrhage
• Intervention / Treatment: Drug: Fibrinogen Concentrate; Other: Cryoprecipitate

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Gold Coast, Queensland, Australia, 4215
      • Gold Coast University Hospital
    • Townsville, Queensland, Australia, 4814
      • Townsville Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult affected by Trauma (>18yrs) and
2. Judged to have significant haemorrhage or
3. Predicted to require significant transfusion with ABC Score ≥ 2 or by treating clinician judgement

Exclusion Criteria:

1. Injury judged incompatible with survival
2. Pregnancy
3. Known objection to blood products
4. Previous Fibrinogen replacement this admission
5. Pre-Trauma Centre fibrinogen replacement
6. Participation in competing study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fibrinogen Concentrate; Fibrinogen Replacement using Fibrinogen Concentrate as per ROTEM guided treatment algorithm [FIBTEM ≤ A5 10mm]	Drug: Fibrinogen Concentrate; Fibrinogen Replacement using Fibrinogen Concentrate as per ROTEM guided treatment algorithm [FIBTEM ≤ A5 10mm] FIBTEM A5 0mm (Flat Line) = 6g FC FIBTEM A5 1 - 4mm = 5g FC FIBTEM A5 5 - 6mm = 4g FC FIBTEM A5 7 - 8mm = 3g FC FIBTEM A5 9 - 10mm = 2g FC; Other Names: RIASTAP
Active Comparator: Cryoprecipitate; Fibrinogen replacement using Cryoprecipitate as per ROTEM guided treatment algorithm [FIBTEM A5 ≤ 10mm]	Other: Cryoprecipitate; Fibrinogen replacement using Cryoprecipitate as per ROTEM guided treatment algorithm [FIBTEM A5 ≤ 10mm] FIBTEM A5 0mm (Flat Line) = 20 Units Cryo FIBTEM A5 1- 4mm = 16 Units Cryo FIBTEM A5 5 - 6mm = 14 Units Cryo FIBTEM A5 7 - 8mm = 10 Units Cryo FIBTEM A5 9 - 10mm = 8 Units Cryo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to administration of Fibrinogen Replacement from time of ROTEM analysis indicating fibrinogen supplementation is required First dose of Fibrinogen Concentrate or Cryoprecipitate required	It is anticipated that fibrinogen replacement will occur with 3 hours Fibrinogen replacement will be with either FC or Cryroprecipitate depending on randomisation	3 Hours
Feasibility of administering FC within 30 mins of clinical scenario and ROTEM analysis suggesting Fibrinogen replacement is required	Proportion of patients receiving FC within 30 minutes	3 Hours
Effects on Fibrinogen levels during traumatic haemorrhage as measured by Clauss Fibrinogen	Blood sampling will occur for 7 days after admission/randomisation	7 Days
Effects on Fibrinogen levels during traumatic haemorrhage as measured by FIBTEM	Blood sampling will occur for 7 days after admission/randomisation	7 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfusion Requirements	In number of units of Packed Red Blood Cells, Plasma, FC, Cryoprecipitate, Platelets, Prothrombin Complex Concentrate at 4, 6, 24, 48hrs	48 hours
Duration of bleeding episode or time until surgical control	It is anticipated that haemorrhage control will be achieved within 12 hours	12 hours
Intensive Care Unit Length of stay		1 Year
Hospital Length of Stay		1 Year
Adverse Events	Transfusion related adverse events Sepsis Multiple Organ Failure Acute Renal Failure Thromboembolic Complications	1Year
All cause Mortality	Mortality at 4, 6, 24 hours and up to 90 days	90 Days

Collaborators and Investigators

• Sponsor: Gold Coast Hospital and Health Service
• Collaborators: Emergency Medicine Foundation; National Blood Authority; Australian Red Cross
• Investigators: Principal Investigator: James Winearls, MBBS, Gold Coast University Hospital

Publications and helpful links

General Publications

• Morrow GB, Feller T, McQuilten Z, Wake E, Ariens RAS, Winearls J, Mutch NJ, Laffan MA, Curry N. Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and stability: Results from a laboratory sub-study of the FEISTY trial. Crit Care. 2022 Sep 26;26(1):290. doi: 10.1186/s13054-022-04167-x.
• Winearls J, Wullschleger M, Wake E, Hurn C, Furyk J, Ryan G, Trout M, Walsham J, Holley A, Cohen J, Shuttleworth M, Dyer W, Keijzers G, Fraser JF, Presneill J, Campbell D. Fibrinogen Early In Severe Trauma studY (FEISTY): study protocol for a randomised controlled trial. Trials. 2017 May 26;18(1):241. doi: 10.1186/s13063-017-1980-x.

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Actual): January 20, 2018
• Study Completion (Actual): February 20, 2018

Study Registration Dates

• First Submitted: April 5, 2016
• First Submitted That Met QC Criteria: April 18, 2016
• First Posted (Estimate): April 20, 2016

Study Record Updates

• Last Update Posted (Actual): March 5, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Fibrinogen; Cryoprecipitate
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: FEISTY-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No