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Study Synopsis
Scientific title of clinical study
A multi-centre, randomised, double blind, placebo-controlled trial
evaluating the effects of early administration of fibrinogen
concentrate in adults with major traumatic haemorrhage
Public title of clinical study
A randomised controlled trial to evaluate fibrinogen concentrate
for severe bleeding after injury
Early fibrinogen in major haemorrhage (E-FIT 1)
Protocol Short Title/Acronym
Protocol Version and Date
Sponsor
Funder
Version 1.0
08/09/2015
NHSBT
CSL Behring
Feasibility trial
Multi-centre, interventional, randomised, double-blind,
parallel, placebo controlled trial
Patients will be randomised 1:1 via pre-labelled study
drug packs in ED
The study will be run and conducted in UK
Study design
Health Condition(s) or
Problem(s) Studied
Key inclusion and exclusion
criteria
Major traumatic haemorrhage
Inclusion criteria:
Patients are eligible for this trial if:
1. Consent/assent is obtained (including waiver)
2. The participant is judged to be an adult (age 16 years or
over) and is affected by traumatic injury
3. The participant is deemed by the attending clinician to have
on-going haemorrhagic shock
AND REQUIRES
4. Activation of the local major haemorrhage protocol for
management of severe blood loss and/or transfusion of
emergency (Group O) red cells
Exclusion criteria:
A patient will not be eligible for this study if he/she fulfils one or
more of the following criteria:
1.
2.
3.
4.
5.
The patient has been transferred from another hospital
The trauma leader deems the injury incompatible with life
More than 3 hours have elapsed from the time of injury
Pregnant women
Severe isolated TBI or unsalvageable head injury
Setting
Interventions to be compared
Emergency Departments of participating hospitals
Intervention arm:
Early single intravenous infusion of trial drug (6g fibrinogen
concentrate), within 45 minutes of admission to hospital,
administered as a slow bolus over 5 minutes.
Comparator arm:
Early single intravenous infusion of placebo, within 45 minutes
of admission to hospital, administered as a slow bolus over 5
minutes.
Study hypothesis
Primary outcome measure(s)
Major bleeding after injury is exacerbated by a clotting
abnormality
acute traumatic coagulopathy (ATC). ATC is
characterised by hypofibrinogenaemia and fibrinolysis. Early
replacement of fibrinogen will treat the coagulopathy and may
reduce bleeding and improve outcomes. This study will evaluate
the clinical and laboratory effects of early fibrinogen
supplementation during major traumatic haemorrhage.
(n = 40):
1. Feasibility of administering FgC within 45 minutes of
admission.
2. Proportion of patients with at least one Clauss fibrinogen
level 2 g/L during active haemorrhage.
Key Secondary outcome
measure (s)
1. Transfusion volumes, in numbers of units, for red cells,
plasma, platelets and cryoprecipitate at 3, 6 hours and 24
hours from admission
2. Clauss fibrinogen levels at day 7 post randomisation
3. ROTEM measures of coagulation (EXTEM and FIBTEM,
where available) to day 7 post randomisation
4. Thrombotic events: venous thromboembolism (DVT, PE)
and arterial events (MI, stroke) to day 28 from randomisation
5. Duration of and/or requirement for organ support to day 28
from admission, as defined by the CTCOFR score
6. All-cause mortality (including death from bleeding) at 3, 6
and 24 hours and up to day 28 from admission. Mortality at
1 year by longer term follow up
7. Hospital stay including ICU/HDU stay
8. Quality of life
9. Proportion of patients achieving haemostasis at 3 hours
from admission (defined using a trial specific haemorrhage
assessment tool)
Duration of Study
Duration of set up
6 months to obtain all ethical/regulatory
approvals, finalise contracts, prepare essential documents and
study database and initiate study centres.
Duration of recruitment The trial will recruit over 18 months,
based on an average recruitment rate of 2.5 patients/month.
Duration of follow-up for each participant will be 28 days.
Duration of study close out
6 months to complete all data
cleaning and statistical analysis and site close out.
The planned total trial duration is 30 months.
Countries of recruitment
Target Sample Size
UK
24 patients per arm, 48 patients in total, to allow an extra 20%
for drop out
Date of first enrolment
Anticipated date of enrolment of the first participant will be
December 2015
Ancillary Studies/sub-studies
Fibrinogen is a key coagulation protein, without which stable
clots cannot be formed. Recent advances in scientific evaluation
of clot formation have meant that it is possible to evaluate the
effects of treatments using a microfluidic environment.
This ancillary study will evaluate the effect of FgC on the
formation of clots under shear stress in a microfluidic system.
This will enable the comparison of patients in receipt of FgC
with those who do not receive early fibrinogen supplementation.
This study will be conducted only at centres with sufficient
laboratory haemostasis expertise.
As many as 4 in every 10 patients affected by severe trauma
die from uncontrolled bleeding. Many of these patients are
found to have an abnormality of the clotting system, known as
acute traumatic coagulopathy (ATC). The two most important
abnormalities in ATC are a low fibrinogen and increased clot
breakdown. It has been hypothesised, and there are some nonrandomised studies that show, that treatment of trauma patients
who are bleeding with fibrinogen therapy stops bleeding more
effectively than standard care, reduces transfusion needs and
may reduce death rates.
This study will look at the effects of infusing a drug (fibrinogen
concentrate) which is a concentrated source of fibrinogen, to
adult trauma patients within 45 minutes of admission to hospital.
It has been shown from a large trauma RCT that early treatment
for bleeding has better outcomes. This study will evaluate
whether it is possible to infuse drug within 45 minutes and will
also look at laboratory and clinical outcome measures.
Lay Summary of Study