Early cryoprecipitate in major trauma haemorrhage: CRYOSTAT-2
| ISRCTN | ISRCTN14998314 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN14998314 |
| IRAS number | 210735 |
| ClinicalTrials.gov number | NCT04704869 |
| Secondary identifying numbers | CPMS 34303, IRAS 210735 |
- Submission date
- 19/04/2017
- Registration date
- 24/04/2017
- Last edited
- 16/10/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Injury, Occupational Diseases, Poisoning
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
Contact information
Public
Centre for Trauma Sciences
Blizard Institute
4 Newark Street
London
E1 2AT
United Kingdom
 ORCID ID |
0000-0003-0643-8866 |
|---|---|
| Phone | +44 (0)20 7882 6175 |
| k.brohi@qmul.ac.uk |
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study 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 |
| 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 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 1600 |
| Total final enrolment | 1604 |
| 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 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 centres
London
E1 1BB
United Kingdom
Oxford
OX3 9UD
United Kingdom
Southampton
SO16 6YD
United Kingdom
London
SW17 0QT
United Kingdom
London
W2 1NY
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Cambridge
CB2 0QQ
United Kingdom
Bristol
BS10 5NB
United Kingdom
Middlesbrough
TS4 3BW
United Kingdom
Leeds
LS1 3EX
United Kingdom
Nottingham
NG7 2UH
United Kingdom
Newcastle-upon-Tyne
NE1 4LP
United Kingdom
Hull
HU3 2JZ
United Kingdom
Sheffield
S5 7AU
United Kingdom
Birmingham
B15 2TH
United Kingdom
Preston
PR2 9HT
United Kingdom
Brighton
BN2N 5BE
United Kingdom
Coventry
CV2 2DX
United Kingdom
Stoke on Trent
ST4 6QG
United Kingdom
Manchester
M6 8HD
United Kingdom
Manchester
M13 9WL
United Kingdom
Liverpool
L9 7AL
United Kingdom
De Crespigny Park
Denmark Hill
London
SE5 8AB
United Kingdom
Belfast
BT12 6BA
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Houston
77030
United States of America
Sponsor information
University/education
JRMO
QMUL Innovation Department
5 Walden Street
London
E1 2EF
England
United Kingdom
| Phone | +44 20 7882 7265 |
|---|---|
| sponsorsresp@bartshealth.nhs.uk | |
"ROR" |
https://ror.org/026zzn846 |
Funders
Funder type
Government
Government organisation / National government
- 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
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2023 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer reviewed journal in 2022 |
| IPD sharing plan | The current data sharing plans for the current study are unknown and will 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 |
Additional files
Editorial Notes
16/10/2023: Publication reference added.
13/10/2023: Basic results uploaded.
11/10/2023: The following changes have been made:
1. Protocol and statistical analysis plan uploaded.
2. IRAS and ClinicalTrials.gov numbers added.
19/09/2023: The intention to publish date was changed from 01/10/2022 to 31/12/2023.
07/04/2022: The following changes have been made:
1. The recruitment end date has been changed from 30/06/2020 to 03/11/2021.
2. The overall trial end date has been changed from 28/02/2021 to 30/06/2022 and the plain English summary has been updated to reflect this change.
3. The intention to publish date has been changed from 01/06/2022 to 01/10/2022.
4. The target number of participants has been changed from "Planned Sample Size: 1544; UK Sample Size: 1125" to "Planned Sample Size: 1600" and the total target enrolment has been changed from 1544 to 1600.
5. The total final enrolment number has been added.
6. The trial website has been added.
7. The trial participating centres “Kings College Hospital”, “Royal Victoria Hospital”, "University Hospital of Wales", and “University of Texas Health Science Center, Houston” have been added.
8. The study contact has been updated and the plain English summary has been updated accordingly.
26/03/2019: 22/03/2019: The condition has been changed from "Specialty: Injuries and emergencies, Primary sub-specialty: Injuries and emergencies; UKCRC code/ Disease: Injuries and Accidents/ Injuries involving multiple body regions" to "Major trauma haemorrhage" following a request from the NIHR.
15/06/2018: The following changes have been made:
1. Karim Brohi has been removed as the scientific contact and Joanne Lucas has been added as the public contact.
2. The plain English summary has been updated to reflect these changes.
