Fibrinogen Early In Severe Trauma studY Junior

Study Overview
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Brief Summary
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Haemorrhage in severe trauma is a significant cause of mortality and is potentially the most preventable cause of death in paediatric 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 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

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

Conditions
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Trauma, Hemorrhage, Coagulopathy, Pediatrics

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Child affected by trauma (3 months to 18 years) Judged to have significant haemorrhage OR predicted to require significant transfusion by the treating clinician Activation of Local MHP or transfusion of emergency red blood cells (Pre-hospital or at Trauma Centre) Exclusion Criteria: Injury judged incompatible with survival Randomisation unable to occur within 6 hours of hospital admission Pregnancy Known personal or parental objection to blood products Known coagulation disorder (i.e. haemophilia, von Willebrand disease) Previous dedicated fibrinogen replacement this admission Pre-Trauma Centre dedicated fibrinogen replacement Participation in competing study

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 18 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
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibrinogen Concentrate<br>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 | Drug: Fibrinogen Concentrate<br>* Experimental<br>* Other names: Riastap;|
| Active Comparator: Cryoprecipitate<br>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 | Drug: Cryoprecipitate<br>* Comparator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to administration of fibrinogen replacement from time of identification of hypofibrinogenaemia requiring fibrinogen replacement | Time to fibrinogen replacement | 3 Hours | 

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 | Up to 48 hours after Trauma Unit presentation | 
| Duration of bleeding episode or time until surgical control | Duration bleeding episode | It is anticipated that haemorrhage control will be achieved within 12 hours | 
| Intensive Care Unit LOS | ICU LOS | 1 Year | 
| Hospital LOS | Hospital LOS | 1 Year | 
| Adverse Events | Transfusion related adverse events, Sepsis, Multiple Organ Failure, Acute Renal Failure, Symptomatic Thromboembolic Complications | 1 Year | 
| All Cause Mortality | Mortality at 4, 6, 24 hours and up to 90 days | Up to 90 Days | 
| Functional Outcomes GOS-E Paediatrics | Functional Outcome Measures at 60 and 90 Days | Up to 90 Days | 

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