Clinical trial NCT05449834: Fibrinogen Early In Severe Trauma StudY II
Official title: Fibrinogen Early In Severe Trauma StudY II
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Trauma
Haemorrhagic Shock
Coagulopathy
Keywords: Fibrinogen
Cryoprecipitate
Lead sponsor: Australian and New Zealand Intensive Care Research Centre
Sponsor class: OTHER
Collaborators: name: Blood Synergy Program
name: Australian and New Zealand Intensive Care Society Clinical Trials Group
name: Australasian College for Emergency Medicine
name: Australian Red Cross Lifeblood
name: Australasian Trauma Society
First posted: 2022-07-08
Enrollment: 850
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A prospective phase III, multi-centre, randomised, controlled, two arm parallel, open label trial evaluating the effect of FC compared to standard care (Cryo) in severely injured bleeding adult trauma patients with major haemorrhage and hypofibrinogenemia.
Primary purpose: TREATMENT

Brief summary: Annually over 7000 Australians are treated for severe trauma. Haemorrhage secondary to severe trauma is a major cause of potentially preventable death and poor outcomes in Australian adults. Severe trauma may trigger changes in blood clotting mechanisms and factor levels leading to inhibition of clot formation and reduced clot strength. This results in the inability of the severely injured trauma patient to form adequate clots to help stop bleeding. There is good evidence to suggest the loss of clotting factors during haemorrhage is associated with worse outcomes and it is thought the early replacement of these factors may reduce bleeding and improve patient outcomes. Fibrinogen is a key clotting factor that helps bind clots together and early fibrinogen replacement may improve outcomes.

Currently fibrinogen is replaced using cryoprecipitate, a blood product made from blood donated by healthy donors which is a precious resource. It can take a significant amount of time to administer as it is frozen and stored in the blood bank. Timely administration of cryoprecipitate is difficult as it requires thawing prior to transfusion. The large doses of cryoprecipitate used in traumatic haemorrhage can put strain on local blood banks in supplying requested units in a timely manner. Additionally, the widely dispersed population of Australia introduces logistic challenges to the maintenance of adequate cryoprecipitate stocks to individual hospital blood banks, especially in remote regions. However, cryoprecipitate contains a number of other coagulation factors (not just fibrinogen) that may be instrumental in clot formation and resistance to fibrinolysis.

Fibrinogen concentrate is an alternative product used to assist in blood clotting. It is a dry powder form of fibrinogen and can be reconstituted at the bedside and given quickly. The use of a fibrinogen factor concentrate with a long shelf life that is easy to use has significant implications for both large urban metropolitan areas and remote isolated communities.

The timing and mode of fibrinogen replacement in traumatic haemorrhage has implications for patient outcomes, blood product availability, costs and the national blood supply. Despite the importance of fibrinogen replacement in traumatic haemorrhage, there have been no clinical trials powered for clinical outcomes directly comparing fibrinogen concentrate and cryoprecipitate. FEISTY II will evaluate the efficacy, safety and cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate in trauma patients with major haemorrhage.

FEISTY II is a phase III randomised trial which will enrol 850 patients from Australian and New Zealand major trauma centres, with a primary patient outcome of days alive out of hospital at day 90 after injury. Severely injured trauma patients who require blood transfusion and have evidence of low fibrinogen levels will be randomised to receive either fibrinogen concentrate or standard care with cryoprecipitate


Eligibility criteria: Inclusion Criteria:

1. Adult affected by trauma (≥18yrs)
2. Judged to have active haemorrhage by treating clinician
3. Activation of local MHP and/or Transfusion of Emergency Blood Products
4. FIBTEM A5 ≤ 10mm or TEG FF A5 ≤ 15mm or FibC ≤ 2 g/l

Exclusion Criteria:

1. Injury judged incompatible with survival
2. Randomisation unable to occur within 6 hours of presentation to hospital
3. Known pregnancy
4. Known genetic or drug induced coagulation disorder
5. Known objection to blood products
6. Dedicated prior fibrinogen replacement
7. Participation in a competing study

Primary outcomes:
measure: Days Alive and Out of Hospital at 90 Days
timeFrame: 90 Days
Secondary outcomes:
measure: Number RBC Units at 24 hours
timeFrame: 24 hours
measure: All cause mortality at 90 days
timeFrame: 90 days
measure: All cause mortality at 6 and 24 hours
timeFrame: 24 hours
measure: Death from haemorrhage at 6 and 24 hours
timeFrame: 24 hours
measure: Ventilator free days up to day 28
timeFrame: 28 days
measure: Symptomatic thromboembolic events to 28 days
timeFrame: 28 days
measure: Quality of life at 3, 6 and 12 months
timeFrame: 12 Months
measure: Health and disability at 3, 6 and 12 months
timeFrame: 12 months
measure: Functional outcome (Patients with TBI) at 12 months
timeFrame: 12 months
measure: Organ failure assessment
timeFrame: 28 days
Other outcomes:
Locations:
city: Gold Coast
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
Study officials:
affiliation: Monash University
name: Zoe McQuilten, MBBS
role: PRINCIPAL_INVESTIGATOR
References: