Trauma, Haemorrhage, Coagulopathy
Conditions
Keywords
Fibrinogen, Cryoprecipitate
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
Interventions
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
OTHERCryoprecipitate
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
Sponsors
Emergency Medicine Foundation
National Blood Authority
Australian Red Cross
Gold Coast Hospital and Health Service
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to administration of Fibrinogen Replacement from time of ROTEM analysis indicating fibrinogen supplementation is required First dose of Fibrinogen Concentrate or Cryoprecipitate required | 3 Hours | It is anticipated that fibrinogen replacement will occur with 3 hours Fibrinogen replacement will be with either FC or Cryroprecipitate depending on randomisation |
| Feasibility of administering FC within 30 mins of clinical scenario and ROTEM analysis suggesting Fibrinogen replacement is required | 3 Hours | Proportion of patients receiving FC within 30 minutes |
| Effects on Fibrinogen levels during traumatic haemorrhage as measured by Clauss Fibrinogen | 7 Days | Blood sampling will occur for 7 days after admission/randomisation |
| Effects on Fibrinogen levels during traumatic haemorrhage as measured by FIBTEM | 7 Days | Blood sampling will occur for 7 days after admission/randomisation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 1Year | Transfusion related adverse events Sepsis Multiple Organ Failure Acute Renal Failure Thromboembolic Complications |
| Transfusion Requirements | 48 hours | In number of units of Packed Red Blood Cells, Plasma, FC, Cryoprecipitate, Platelets, Prothrombin Complex Concentrate at 4, 6, 24, 48hrs |
| All cause Mortality | 90 Days | Mortality at 4, 6, 24 hours and up to 90 days |
| Duration of bleeding episode or time until surgical control | 12 hours | It is anticipated that haemorrhage control will be achieved within 12 hours |
| Intensive Care Unit Length of stay | 1 Year | — |
| Hospital Length of Stay | 1 Year | — |
Countries
Australia
Outcome results
None listed