Fibrinogen Early In Severe Trauma studY

Study Overview
=================
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

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

Conditions
-----------------
Trauma, Haemorrhage, Coagulopathy

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fibrinogen Concentrate<br>Fibrinogen Replacement using Fibrinogen Concentrate as per ROTEM guided treatment algorithm [FIBTEM ≤ A5 10mm] | Drug: Fibrinogen Concentrate<br>* 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<br>* Other names: RIASTAP;|
| Active Comparator: Cryoprecipitate<br>Fibrinogen replacement using Cryoprecipitate as per ROTEM guided treatment algorithm [FIBTEM A5 ≤ 10mm] | Other: Cryoprecipitate<br>* 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<br>|

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 | 

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