Plain English Summary
Background and study aims
Major trauma is damage caused to the body by an external source, such as a car accident or stabbing. It accounts for a significant number of deaths in the UK, and is one of the most frequent causes of death in people under the age of 45. One of the most common causes of death in trauma patients is uncontrolled bleeding. At present, standard treatment for severe bleeding involves giving patients blood transfusions. Until recently one out of every two people who received a massive blood transfusion (more than 10 pints) would die from their injuries. Two important studies involving bleeding trauma patients have been conducted in the last five years showing that early intervention is more effective after injury and may help save lives. Patients who have severe bleeding after injury develop a problem with their clotting system which means that they tend to bleed more. One of the main problems is due to low levels of fibrinogen, a clotting protein normally circulating in the bloodstream. Fibrinogen acts as the ‘glue’ which holds a blood clot together and at low levels, blood clots don’t form properly and bleeding can continue. Cryoprecipitate is a frozen blood component prepared from plasma (the liquid part of blood) and rich in fibrinogen. By giving patients cryoprecipitate early on to raise fibrinogen levels in bleeding trauma patients it may be possible to make blood clots more stable and reduce bleeding. The aim of this study is to find out whether or not giving cryoprecipitate treatment reduces death rates in trauma patients with severe bleeding.
Who can participate?
Trauma patients with severe bleeding who are taken to a Major Trauma Centre
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group receive standard care, which involves being treated with large blood transfusions through a drip. Those in the second group are treated with cryoprecipitate before they are given the blood transfusions. Participants in both groups are followed up for survival rates until study day 28 and then for up to one year using the Office for National Statistics. The Trauma Audit Research Network administers questionnaires to assess quality of life six months after injury.
What are the possible benefits and risks of participating?
There is a small chance that patients receiving cryoprecipitate early may raise their blood fibrinogen level higher than those receiving standard care and this may increase the risk of clots such as deep vein thrombosis (DVT), clots in the lungs, heart attacks and strokes. However, in small trauma studies to date there has been no evidence of an increased risk of developing clots. There are no anticipated additional risks associated with participating in this trial.
Where is the study run from?
23 NHS hospitals with Major Trauma Centres in England (UK)
When is the study starting and how long is it expected to run for?
February 2017 to June 2022
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Professor Karim Brohi
k.brohi@qmul.ac.uk
Study website
Contact information
Type
Public
Contact name
Prof Karim Brohi
ORCID ID
http://orcid.org/0000-0003-0643-8866
Contact details
Centre for Trauma Sciences
Blizard Institute
4 Newark Street
London
E1 2AT
United Kingdom
+44 (0)20 7882 6175
k.brohi@qmul.ac.uk
Additional identifiers
EudraCT/CTIS number
Nil known
IRAS number
210735
ClinicalTrials.gov number
NCT04704869
Protocol/serial number
CPMS 34303, IRAS 210735
Study information
Scientific title
CRYOSTAT-2: A multi-centre, randomised, controlled trial evaluating the effects of early high-dose cryoprecipitate in adult patients with major trauma haemorrhage requiring major haemorrhage protocol (MHP) activation
Acronym
CRYOSTAT-2
Study hypothesis
The primary aim of this study is to test whether early high-dose fibrinogen supplementation with cryoprecipitate reduces all-cause mortality at 28 days in adult trauma patients with haemorrhagic shock and active bleeding.
Ethics approval(s)
South Central REC C - Oxford, 12/04/2017, ref: 17/SC/0164
Study design
Randomized controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Hospital
Study type
Treatment
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Major trauma haemorrhage
Intervention
Adult Trauma patients admitting to recruiting Major Trauma Centres, who are eligible for the trial, will be entered into the trial using an emergency waiver of consent. Patients on arrival will be incapacitated as a result of their injuries and ongoing bleeding and therefore will be unable to provide informed consent. Professional consultees (physicians who are not part of the study team) will provide approval for the patient to continue in the study until such time it is possible to speak with the patient and/or their next of kin.
Participants will be randomised to one of two groups using opaque sealed randomisation envelopes to enable rapid access and timely recruitment in the emergency setting.
Control group: Participants receive care using the tandard major haemorrhage protocol only. This involves administering red blood cells, fresh frozen plasma and platelets following a major haemorrhage protocol (MHP) as part of a balanced resuscitation.
Intervention group: Participants receive early cryoprecipitate – 3 pools (equivalent to 15 single units cryoprecipitate or 6g fibrinogen supplementation), infused as rapidly as possible, within 90 minutes of admission in addition to the standard (local) major haemorrhage
Patients will be followed up for death up until study day 28 and for up to 1 year post admission with the Office for National Statistics. Follow up for quality of life will be undertaken at 6 months post injury via the Trauma Audit Research Network.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Phase III
Drug/device/biological/vaccine name(s)
Cryoprecipitate
Primary outcome measure
All-cause mortality at 28 days as documented and confirmed in the patients medical notes by attending physicians. The primary cause of death will be documented and if possible categorised according to the following clinical causes:
1. Uncontrolled bleeding
2. Vascular occlusion (myocardial infarction, stroke)
3. Pulmonary embolism
4. Multi-organ failure
5. Traumatic brain injury
6. Multiple injury
7. Sepsis
8. Other (reason)
Secondary outcome measures
1. All-cause mortality (including death from bleeding) at 6 hours, 24 hours, 6 months and 12 months from admission as record in the patients medical notes during their admission and captured by the Office for National Statistics for up to 1 year post admission
2. Death from bleeding at 6 hours and 24 hours as recorded in the patients medical notes
3. Transfusion requirements, in numbers of units, for RBC, platelets, FFP & cryoprecipitate at 24 hours from admission, including pre-hospital transfusion as recorded in the patients medical notes
4. Destination of participant at time of discharge from hospital as recorded by the research team
5. Quality of life measures: EQ5D-5L and Glasgow Outcome Score at discharge and 6 months after injury captured by patient questionnaires administrated by the Trauma Audit Research Network
6. Hospital resource use up to discharge or day 28, including blood transfusions, surgical procedures, ventilator days, hours spent in critical care and in-patient stays measured by clinical data captured by the research teams in the Case Report Forms
Overall study start date
07/02/2017
Overall study end date
30/06/2022
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. The participant is judged to be an adult (according to local practice, e.g. 16 years or older in UK) and has sustained severe traumatic injury
2. Deemed by the attending clinician to have on-going active haemorrhage
3. Requires activation of the local major haemorrhage protocol for management of severe blood loss
4. Has started or received at least one unit of any blood component
Participant type(s)
Patient
Age group
Adult
Sex
Both
Target number of participants
Planned Sample Size: 1600
Total final enrolment
1604
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
Recruitment start date
01/07/2017
Recruitment end date
03/11/2021
Locations
Countries of recruitment
England, Northern Ireland, United Kingdom, United States of America, Wales
Study participating centre
Royal London Hospital
Whitechapel
London
E1 1BB
United Kingdom
Study participating centre
John Radcliffe Hospital
Headley Way
Oxford
OX3 9UD
United Kingdom
Study participating centre
Southampton Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Study participating centre
St George’s Hospital
Blackshaw Road
London
SW17 0QT
United Kingdom
Study participating centre
St Mary’s Hospital
Praed Street
London
W2 1NY
United Kingdom
Study participating centre
Derriford Hospital
Derriford Road
Plymouth
PL6 8DH
United Kingdom
Study participating centre
Addenbrooke’s Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Study participating centre
Southmead Hospital
Southmead Road
Bristol
BS10 5NB
United Kingdom
Study participating centre
James Cook University Hospital
Marton Road
Middlesbrough
TS4 3BW
United Kingdom
Study participating centre
Leeds General Infirmary
Great George St
Leeds
LS1 3EX
United Kingdom
Study participating centre
Queen’s Medical Centre
Derby Road
Nottingham
NG7 2UH
United Kingdom
Study participating centre
Royal Victoria Infirmary
Queen Victoria Road
Newcastle-upon-Tyne
NE1 4LP
United Kingdom
Study participating centre
Hull Royal Infirmary
Anlaby Road
Hull
HU3 2JZ
United Kingdom
Study participating centre
Northern General Hospital
Herries Road
Sheffield
S5 7AU
United Kingdom
Study participating centre
Queen Elizabeth Hospital
Mindelsohn Way
Birmingham
B15 2TH
United Kingdom
Study participating centre
Royal Preston Hospital
Sharoe Green Lane
Preston
PR2 9HT
United Kingdom
Study participating centre
Royal Sussex County Hospital
Eastern Road
Brighton
BN2N 5BE
United Kingdom
Study participating centre
University Hospital
Clifford Bridge Road
Coventry
CV2 2DX
United Kingdom
Study participating centre
University Hospital of North Staffordshire
Newcastle Road
Stoke on Trent
ST4 6QG
United Kingdom
Study participating centre
Salford Royal Hospital
Scott Lane
Manchester
M6 8HD
United Kingdom
Study participating centre
Manchester Royal Infirmary
Oxford Road
Manchester
M13 9WL
United Kingdom
Study participating centre
University Hospital Aintree
Lower Lane
Liverpool
L9 7AL
United Kingdom
Study participating centre
Kings College Hospital
Mapother House
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom
Study participating centre
Royal Victoria Hospital
274 Grosvenor Rd
Belfast
BT12 6BA
United Kingdom
Study participating centre
University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom
Study participating centre
University of Texas Health Science Center, Houston
7000 Fannin Street
Houston
77030
United States of America
Sponsor information
Organisation
Queen Mary University of London
Sponsor details
JRMO
QMUL Innovation Department
5 Walden Street
London
E1 2EF
England
United Kingdom
+44 20 7882 7265
sponsorsresp@bartshealth.nhs.uk
Sponsor type
University/education
Website
ROR
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal in 2022
Intention to publish date
31/12/2023
Individual participant data (IPD) sharing plan
The current data sharing plans for the current study are unknown and will be made available at a later date.
IPD sharing plan summary
Data sharing statement to be made available at a later date
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol file | version 4.0 | 15/02/2022 | 11/10/2023 | No | No |
| Statistical Analysis Plan | version 2.0 | 20/05/2022 | 11/10/2023 | No | No |
| Basic results | 13/10/2023 | No | No | ||
| Results article | 12/10/2023 | 16/10/2023 | Yes | No |