Condition category
Injury, Occupational Diseases, Poisoning
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Background and study aims
Injury is a leading cause of death and disability worldwide. Around 7,800 people die in England every year, and many thousands more are left severely disabled. Uncontrolled bleeding is the main cause of death in 40% of cases. Transfusion therapy (which includes giving patients additional red blood cells, fresh frozen plasma, platelets and cryoprecipitate) is an important part of emergency treatment for major bleeding. Although the standard transfusion therapy is routinely followed in all hospitals, we are not sure whether by giving an additional source of fibrinogen, with a drug called fibrinogen concentrate, as quickly as possible works better than standard practice. The main objective of this clinical trial is to test whether it is possible to give fibrinogen concentrate within 45 minutes of admission to hospital to adult trauma patients with severe bleeding.

Who can participate?
People aged at least 16 with severe bleeding and shock.

What does the study involve?
Patients are randomly allocated to one of two groups. Those in group 1 are given 6g of fibrinogen concentrate within 45 minutes of being admitted to hospital, in addition to standard major haemorrhage therapy. Those in group 2 are given a placebo in additional to the standard major haemorrhage therapy. The effects of the two treatment regimens are then compared, focusing in particular on differences in blood test results and on clinical outcomes such as bleeding and organ failure.

What are the possible benefits and risks of participating?
The potential benefits associated of this study include early stopping of major bleeding which may lead to reduced need for transfusions of red cells, plasma or platelets. This, in turn, may lead to improved clinical outcomes such as reduced stays on intensive care, or total in hospital stay. It may have an effect on reducing the number of deaths, but this is not yet known. The theoretical risk of giving higher dose fibrinogen is to cause an increased chance of thromboembolism (blood clot) both in the vein (such as a pulmonary embolism or deep venous thrombosis) or in the artery (such as a heart attack or a stroke).

Where is the study run from?
The John Radcliffe Hospital (lead centre), the Royal London Hospital, Southampton General Hospital and the Edinburgh Royal Infirmary (UK)

When is the study starting and how long is it expected to run for?
October 2015 to April 2017

Who is funding the study?
CSL Behring

Who is the main contact?
Dr Nicola Curry

Trial website

Contact information



Primary contact

Dr Nicola Curry


Contact details

University of Oxford
Churchill Hospital
Old Road
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A multi-centre, randomised, double blind, placebo-controlled trial evaluating the effects of early administration of fibrinogen concentrate in adults with major traumatic haemorrhage.


E-FIT 1 v1.0

Study hypothesis

The main objective of this clinical trial is to test whether it is possible to give fibrinogen concentrate within 45 minutes of admission to hospital to adult trauma patients with severe bleeding.

Ethics approval

Oxford REC C, 15/07/2015, ref: 15/SC/0316

Study design

Randomised controlled trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use contact details to request a participant information sheet


Topic: Injuries and Emergencies, Haematology; Subtopic: Injuries and Emergencies (All Subtopics), Haematology (All Subtopics); Disease: Injuries and Emergencies, Non-malignant Haematology


Early supplementation of Fibrinogen concentrate (FgC) in patients with major traumatic haemorrhage. Patients will be randomised to receive either 6g fibrinogen concentrate or placebo within 45 minutes of admission to hospital.

Intervention type



Drug names

Primary outcome measure

Current primary outcome measure as of 24/08/2018:
1. Mean fibrinogen levels over time by treatment arm at admission, At 2 hours from admission during first active haemorrhage and 7 days from admission

Previous primary outcome measures:
1. Feasibility of administering fibrinogen concentrate within 45 minutes of admission.
2. Proportion of patients with at least one Clauss fibrinogen level ≥ 2 g/L during active haemorrhage.

Secondary outcome measures

Current secondary outcome measure as of 24/08/2018:
1. Transfusion volumes, in numbers of units, for red cells, plasma, platelets and cryoprecipitate at 3, 6 hours and 24 hours from admission

Previous secondary outcome measures:
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: clinically apparent 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 at 28 day from admission
9. Proportion of patients achieving haemostasis at 3 hours from admission (defined using a trial specific haemorrhage assessment tool)

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Written informed consent or agreement, or waiver of consent, is obtained before any study related activity
2. The participant is judged to be an adult (aged 16 years or over) and is affected by traumatic injury
3. The participant is deemed by the attending clinician to have ongoing active haemorrhage with shock
4. Activation of the local major haemorrhage protocol for management of severe blood loss and/or transfusion of emergency (Group O) red cells

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. The participant has been transferred from another hospital
2. The trauma team leader deems the patient inappropriate for the trial i.e. injuries deemed to be incompatible with life
3. More than 3 hours have elapsed from the time of injury
4. The participant is pregnant
5. Severe isolated TBI or unsalvageable head injury

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

John Radcliffe Hospital (lead centre)
United Kingdom

Trial participating centre

Royal London Hospital
E1 1BB
United Kingdom

Trial participating centre

Southampton General Hospital
SO16 6YD
United Kingdom

Trial participating centre

Edinburgh Royal Infirmary
EH16 4SA
United Kingdom

Sponsor information


NHS Blood and Transplant (NHSBT)

Sponsor details

NHSBT Clinical Trials Unit
Long Road
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

CSL Behring

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

The final study data set will be analysed and results published as soon as possible following completion of study follow up, final data checks and database lock. Individual Clinicians must not publish data concerning their patients that are directly relevant to questions posed by the trial until the Trial Management Group has published its report. The Trial Management Group will form the basis of the Writing Committee and will advise on the nature of publications.

Intention to publish date


Participant level data

Available on request

Basic results (scientific)

See additional file (ISRCTN67540073_BasicResults_24Aug18)

Publication list

2018 results in

Publication citations

Additional files

Editorial Notes

24/08/2018: The following changes have been made: 1. The outcome measures were updated. 2. The intention to publish date was added. 3. The basic results of this trial have been uploaded as an additional file. 4. Publication reference added.