Evaluating the effects of early administration of fibrinogen concentrate in adults with major traumatic haemorrhage.

ISRCTN	ISRCTN67540073
DOI	https://doi.org/10.1186/ISRCTN67540073
Protocol serial number	19181
Sponsor	NHS Blood and Transplant (NHSBT)
Funder	CSL Behring

Submission date: 05/08/2015
Registration date: 06/08/2015
Last edited: 12/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Injury, Occupational Diseases, Poisoning

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

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

Contact information

Dr Nicola Curry
Scientific

University of Oxford
Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom

ORCID ID	0000-0002-3849-0688

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
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.
Study acronym	E-FIT 1 v1.0
Study objectives	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(s)	Oxford REC C, 15/07/2015, ref: 15/SC/0316
Health condition(s) or problem(s) studied	Topic: Injuries and Emergencies, Haematology; Subtopic: Injuries and Emergencies (All Subtopics), Haematology (All Subtopics); Disease: Injuries and Emergencies, Non-malignant Haematology
Intervention	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	Other
Primary outcome measure(s)	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.
Key secondary outcome measure(s)	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)
Completion date	30/04/2017

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	48
Key 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 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
Key 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
Date of first enrolment	01/10/2015
Date of final enrolment	31/03/2017

Locations

Countries of recruitment

United Kingdom
England
Scotland

Study participating centres

John Radcliffe Hospital (lead centre)

Oxford
OX3 9DU
United Kingdom

Royal London Hospital

London
E1 1BB
United Kingdom

Southampton General Hospital

Southampton
SO16 6YD
United Kingdom

Edinburgh Royal Infirmary

Edinburgh
EH16 4SA
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	18/06/2018		Yes	No
Protocol article		26/05/2017	12/09/2023	Yes	No
Basic results		24/08/2018	24/08/2018	No	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Additional files

ISRCTN67540073_BasicResults_24Aug18.pdf: Uploaded 24/08/2018

Editorial Notes

12/09/2023: Publication reference added.
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.