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
Type
Scientific
Primary contact
Dr Nicola Curry
ORCID ID
http://orcid.org/0000-0002-3849-0688
Contact details
University of Oxford
Churchill Hospital
Old Road
Oxford
OX3 7LE
United Kingdom
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
19181
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.
Acronym
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
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details to request a participant information sheet
Condition
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
Phase
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
01/10/2015
Overall trial end date
30/04/2017
Reason abandoned (if study stopped)
Eligibility
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
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
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
48
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
01/10/2015
Recruitment end date
31/03/2017
Locations
Countries of recruitment
United Kingdom
Trial participating centre
John Radcliffe Hospital (lead centre)
Oxford
OX3 9DU
United Kingdom
Trial participating centre
Royal London Hospital
London
E1 1BB
United Kingdom
Trial participating centre
Southampton General Hospital
Southampton
SO16 6YD
United Kingdom
Trial participating centre
Edinburgh Royal Infirmary
Edinburgh
EH16 4SA
United Kingdom
Funders
Funder type
Industry
Funder name
CSL Behring
Alternative name(s)
Funding Body Type
private sector organisation
Funding Body Subtype
corporate
Location
United States of America
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
18/06/2018
Participant level data
Available on request
Basic results (scientific)
See additional file (ISRCTN67540073_BasicResults_24Aug18)
Publication list
2018 results in https://www.ncbi.nlm.nih.gov/pubmed/29914530
Publication citations
Additional files
- ISRCTN67540073_BasicResults_24Aug18.pdf Uploaded 24/08/2018