Fibrinogen Early In Severe Trauma studY Junior

Phase 2

• Conditions: Trauma; Hemorrhage; Coagulopathy; Pediatrics
• Interventions: Drug: Cryoprecipitate; Drug: Fibrinogen Concentrate

• Registration Number: NCT03508141
• Lead Sponsor: Gold Coast Hospital and Health Service

Brief Summary

1. Haemorrhage in severe trauma is a significant cause of mortality and is potentially the most preventable cause of death in paediatric trauma patients

2. Trauma Induced Coagulopathy (TIC) is a complex coagulopathy associated with severe trauma

3. Hypo/dysfibrinogenaemia plays an important role in TIC

4. Early replacement of fibrinogen may improve outcomes

5. Fibrinogen replacement is potentially inadequate in standard fixed ratio Major Haemorrhage Protocols (MHP) utilising Plasma and/or Cryoprecipitate

6. The majority of centres utilise cryoprecipitate for additional fibrinogen supplementation as part of a MHP

7. Cryoprecipitate administration is often delayed (between 60 - 120 minutes) in a fixed ratio MHP

8. It is clear early intervention in severe traumatic haemorrhage is associated with improved outcomes - CRASH 2 and PROPPR studies

9. Increasing interest in the use of Fibrinogen Concentrate (FC) in severe bleeding but not supported by high level evidence

10. 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

12. No previous studies comparing FC and Cryoprecipitate in bleeding paediatric trauma patients 13. Fibrinogen supplementation will be guided by an accepted ROTEM targeted treatment algorithm 14. Pilot, multi-centre randomised controlled trial comparing FC to Cryoprecipitate (current standard practise in fibrinogen supplementation) 15. Hypothesis: Fibrinogen replacement in severe traumatic haemorrhage can be achieved quicker with a more predictable dose response using Fibrinogen Concentrate compared to Cryoprecipitate 16. It is imperative that robust and clinically relevant trials are performed to investigate fibrinogen supplementation in paediatric trauma patients before widespread adoption makes performing such studies unfeasible

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-03-23
• Study First Submitted QC: 2018-04-16
• Study First Posted: 2018-04-25
• Study Start: 2018-07-01
• Status Verified: 2020-06
• Last Update Submitted: 2020-06-25
• Last Update Posted: 2020-06-29
• Primary Completion: 2021-06-30
• Study Completion: 2021-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

1. Child affected by trauma (3 months to 18 years)
2. Judged to have significant haemorrhage OR predicted to require significant transfusion by the treating clinician
3. Activation of Local MHP or transfusion of emergency red blood cells (Pre-hospital or at Trauma Centre)

Exclusion Criteria

1. Injury judged incompatible with survival
2. Randomisation unable to occur within 6 hours of hospital admission
3. Pregnancy
4. Known personal or parental objection to blood products
5. Known coagulation disorder (i.e. haemophilia, von Willebrand disease)
6. Previous dedicated fibrinogen replacement this admission
7. Pre-Trauma Centre dedicated fibrinogen replacement
8. Participation in competing study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cryoprecipitate	Cryoprecipitate	Fibrinogen Replacement using Cryoprecipitate as per ROTEM (FIBTEM) FIBTEM A5 0mm = 6ml/kg Cryoprecipitate FIBTEM A5 1-4mm = 5ml/kg Cryoprecipitate FIBTEM A5 5-6mm = 4ml/kg Cryoprecipitate FIBTEM A5 7-8mm = 3ml/kg Cryoprecipitate FIBTEM A5 9-10mm = 2ml/kg Cryoprecipitate
Fibrinogen Concentrate	Fibrinogen Concentrate	Fibrinogen Replacement using Fibrinogen Concentrate as per ROTEM (FIBTEM) FIBTEM A5 0mm = 60mg/kg FC FIBTEM A5 1-4mm = 50mg/kg FC FIBTEM A5 5-6mm = 40mg/kg FC FIBTEM A5 7-8mm = 30mg/kg FC FIBTEM A5 9-10mm = 20mg/kg FC

Primary Outcome Measures

Name	Time	Method
Time to administration of fibrinogen replacement from time of identification of hypofibrinogenaemia requiring fibrinogen replacement	3 Hours	Time to fibrinogen replacement

Secondary Outcome Measures

Name	Time	Method
Transfusion Requirements	Up to 48 hours after Trauma Unit presentation	In number of units of Packed Red Blood Cells, Plasma, FC, Cryoprecipitate, Platelets, Prothrombin Complex Concentrate at 4, 6, 24, 48hrs
Adverse Events	1 Year	Transfusion related adverse events, Sepsis, Multiple Organ Failure, Acute Renal Failure, Symptomatic Thromboembolic Complications
Duration of bleeding episode or time until surgical control	It is anticipated that haemorrhage control will be achieved within 12 hours	Duration bleeding episode
Intensive Care Unit LOS	1 Year	ICU LOS
All Cause Mortality	Up to 90 Days	Mortality at 4, 6, 24 hours and up to 90 days
Functional Outcomes GOS-E Paediatrics	Up to 90 Days	Functional Outcome Measures at 60 and 90 Days
Hospital LOS	1 Year	Hospital LOS

Trial Locations

Locations (10)

Royal Brisbane and Women's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Cairns Hospital; 🇦🇺 Cairns, Queensland, Australia

Gold Coast University Hospital; 🇦🇺 Gold Coast, Queensland, Australia

Townsville Hospital; 🇦🇺 Townsville, Queensland, Australia

Lady Cilento Children's Hospital; 🇦🇺 Brisbane, Queensland, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Westmead Childrens Hospital; 🇦🇺 Sydney, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

Rockhampton Hospital; 🇦🇺 Rockhampton, Queensland, Australia

Mackay Base Hospital; 🇦🇺 Mackay, Queensland, Australia