Fibrinogen Early In Severe Trauma studY

NCT02745041 | Completed Phase 2 DMC

• 1 other identifier: FEISTY-1
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

• 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

Conditions

Trauma; Haemorrhage; Coagulopathy

Keywords

Fibrinogen; Cryoprecipitate

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• Transfusion Requirements

  48 hours

• Duration of bleeding episode or time until surgical control

  12 hours

• Intensive Care Unit Length of stay

  1 Year

• Hospital Length of Stay

  1 Year

• Adverse Events

  1Year

Study Arms (2)

Fibrinogen Concentrate

EXPERIMENTAL

Fibrinogen Replacement using Fibrinogen Concentrate as per ROTEM guided treatment algorithm \[FIBTEM ≤ A5 10mm\]

Drug: Fibrinogen Concentrate

Cryoprecipitate

ACTIVE COMPARATOR

Fibrinogen replacement using Cryoprecipitate as per ROTEM guided treatment algorithm \[FIBTEM A5 ≤ 10mm\]

Other: Cryoprecipitate

Interventions

Fibrinogen Concentrate DRUG

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

Also known as: RIASTAP

Fibrinogen Concentrate

Cryoprecipitate OTHER

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

Cryoprecipitate

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Injury judged incompatible with survival
• Pregnancy
• Known objection to blood products
• Previous Fibrinogen replacement this admission
• Pre-Trauma Centre fibrinogen replacement
• Participation in competing study

Sponsors & Collaborators

• Gold Coast Hospital and Health Service: lead
• Emergency Medicine Foundation: collaborator
• National Blood Authority: collaborator
• Australian Red Cross: collaborator

Study Sites (4)

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

Location

Gold Coast University Hospital

Gold Coast, Queensland, 4215, Australia

Location

Townsville Hospital

Townsville, Queensland, 4814, Australia

Location

Related Publications (2)

• 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.

  PMID: 36163263 DERIVED

• 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.

  PMID: 28549445 DERIVED

MeSH Terms

Conditions

Wounds and Injuries; Hemorrhage; Hemostatic Disorders

Interventions

Fibrinogen; cryoprecipitate coagulum

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Acute-Phase Proteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Blood Coagulation Factors; Protein Precursors; Biological Factors

Study Officials

• James Winearls, MBBS

  Gold Coast University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Intensivist, GCUH ICU

Study Record Dates

• First Submitted: April 5, 2016
• First Posted: April 20, 2016
• Study Start: December 1, 2016
• Primary Completion: January 20, 2018
• Study Completion: February 20, 2018
• Last Updated: March 5, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)