Fibrinogen Early In Severe Trauma studY

Phase 2

Completed

• Conditions: Haemorrhage; Coagulopathy; Trauma
• Interventions: Other: Cryoprecipitate; Drug: Fibrinogen Concentrate

• Registration Number: NCT02745041
• Lead Sponsor: Gold Coast Hospital and Health Service

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-04-05
• Study First Submitted QC: 2016-04-18
• Study First Posted: 2016-04-20
• Study Start: 2016-12
• Primary Completion: 2018-01-20
• Study Completion: 2018-02-20
• Status Verified: 2018-03
• Last Update Submitted: 2018-03-02
• Last Update Posted: 2018-03-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cryoprecipitate	Cryoprecipitate	Fibrinogen replacement using Cryoprecipitate as per ROTEM guided treatment algorithm \[FIBTEM A5 ≤ 10mm\]
Fibrinogen Concentrate	Fibrinogen Concentrate	Fibrinogen Replacement using Fibrinogen Concentrate as per ROTEM guided treatment algorithm \[FIBTEM ≤ A5 10mm\]

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Intensive Care Unit Length of stay	1 Year
Duration of bleeding episode or time until surgical control	12 hours	It is anticipated that haemorrhage control will be achieved within 12 hours
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
Adverse Events	1Year	Transfusion related adverse events Sepsis Multiple Organ Failure Acute Renal Failure Thromboembolic Complications
All cause Mortality	90 Days	Mortality at 4, 6, 24 hours and up to 90 days
Hospital Length of Stay	1 Year

Trial Locations

Locations (4)

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

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia

Townsville Hospital; 🇦🇺 Townsville, Queensland, Australia

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