Trial aims
This study will investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units – 6g fibrinogen) of cryoprecipitate on 28 day mortality.
Worldwide, it is estimated that 5.8 million people die annually from trauma with most of those who die under the age of 45. For the same age group that is more than cancer, HIV/AIDS and heart disease combined.
Patient count so far: Email the team
One of the most common causes of death in trauma patients is uncontrolled bleeding. At present, standard treatment for severe bleeding involves rapid infusion of red blood cells and blood components e.g. plasma and platelets, in large volumes.
Until recently, one in 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 and rich in fibrinogen. By transfusing cryoprecipitate early to replace fibrinogen levels in bleeding trauma patients, we believe blood clots will be more stable, reducing bleeding and consequently the number of deaths.
CRYOSTAT 2 is an international, pragmatic, multi-centre, parallel group, randomised controlled trial, which will run at all of the major trauma centres in England and at 8 international centres. It is designed to answer a simple research question of whether the addition of early cryoprecipitate to the current standard of care Major Haemorrhage Protocol (MHP) improves survival from major trauma haemorrhage.
Bleeding accounts for 40% of all deaths from trauma, many within hours of injury. Our recent NIHR Programme Grant for Applied Research found that approximately 7,780 people nationally suffer major haemorrhage each year, of whom an estimated 2,800 will die, at a total cost of nearly £150m to the NHS [Campbell et al, 2015].
Fibrinogen is the key pro-coagulant factor needed for stable clot formation and the earliest clotting protein to fall during active major bleeding [Hiippala et al, 1995]. 25% of all trauma patients have abnormal blood clotting, which causes higher rates of major haemorrhage and four fold increased risk of death. The primary clotting abnormalities in trauma are: increased clot breakdown and low fibrinogen levels.
The CRASH-2 trial has shown that early treatment with tranexamic acid prevents clot breakdown and reduces mortality from trauma haemorrhage [Shakur et al, 2010]. The results of our national observational trauma transfusion study found cryoprecipitate is administered late during the MHP, on average three hours after arrival.
In CRYOSTAT-1 we have shown that early replacement of fibrinogen with cryoprecipitate is able to rapidly restore fibrinogen levels and may halve mortality from trauma haemorrhage [Curry N et al, 2015]. Following on from this work, CRYOSTAT-2 will evaluate whether early administration of high-dose cryoprecipitate, in addition to standard major haemorrhage therapy, improves survival from traumatic bleeding.
The results from this trial will immediately inform transfusion resuscitation practice both nationally and internationally.
This study will investigate the effects of early fibrinogen supplementation in the form of 3 pools (15 units – 6g fibrinogen) of cryoprecipitate on 28 day mortality.
CRYOSTAT 2 is a multi-centre interventional parallel group randomised controlled trial.
The study will be managed by the NHS Blood & Transplant Clinical Trials Unit with UK and International sites.
Patients are eligible for this trial if:
A patient will not be eligible for this study if he/she fulfils one or more of the following criteria:
Our primary outcome is all-cause mortality at 28 days.
Additional secondary measures include:
Queen Mary University of London (QMUL) is the Sponsor for this clinical trial which is based in the United Kingdom and has delegated overall management of this study to the Clinical Trials Unit at NHS Blood & Transplant, and will act as joint data controllers. This means that we are responsible for looking after your information and using it properly.
Your information will only be used by researchers to conduct research in accordance with the UK Policy Framework for Health and Social Care Research.
We will be using information from you and your medical records in order to undertake this trial.
As publicly-funded organisations, we have to ensure that it is in the public interest when we use personally-identifiable information from people who have agreed to take part in research.
With your signed consent, we will keep identifiable information about you for 2 years after the study has finished to allow us to complete analysis of the data that we have collected. After this time your identifiable information will be deleted.
To safeguard your rights, we will use the minimum amount of personally-identifiable information possible.
The personally-identifiable information we will collect are: Name, date of birth, sex, NHS number (or CHI number if you live in Scotland) and postcode. This data is shared with NHS Digital so that we can check on your survival status one year after your injury. For some patients, we will also access information collected by the Trauma Audit & Research Network (TARN, hosted by the University of Manchester) about how you feel about your health six months after your injury. By accessing existing TARN data, it means that we do not need to ask you for the same information twice. NHS Blood & Transplant will have contracts with NHS Digital and The University of Manchester that will ensure the security and integrity of your data at all times. This data will only be shared for this purpose and deleted at the end of the study. It will not be shared with any other organisation or published.
NHS Blood & Transplant will have special permission in place to collect personally identifiable data from those participants who take part in the study but have not signed a consent form (e.g. due to the nature of their injury, or who were discharged prior to consent being taken by the research team for any reason). If you did not sign a consent form and you do not wish for your identifiable data to be used, you can contact us on 01223 588720 or via email cryostat2@nhsbt.nhs.uk
You have the right to access, correct or complete the information you have given us. You also have the right to withdraw from the trial at any time and request that your data be deleted (“right to be forgotten”). If you wish to withdraw, please arrange to speak with the doctor or nurse listed at the bottom of your patient information sheet. After the trial has been completed, we will provide QMUL with an anonymised data set produced by the research. This information will not identify you and cannot be combined with other information in a way that could identify you.
You can find out more about how we use your information in research at https://www.hra.nhs.uk/information-about-patients/ or by contacting the Trial Manager by email at cryostat2@nhsbt.nhs.uk
Under GDPR, all NHS organisations are legally required to appoint a Data Protection Officer (DPO). The DPO for NHS Blood & Transplant is Aaron Powell, the Chief Digital Officer, who is responsible for ensuring that all practices and processes within NHS Blood & Transplant are designed to support people’s privacy and data rights. You can contact the DPO by email at dpofficer@nhsbt.nhs.uk
You can also look at the website of the Information Commissioner (https://ico.org.uk/) for more information on the new GDPR legislation and you have the right to speak to them if you are worried that your data is not being appropriately protected or processed.
You can also Download our Privacy Policy in PDF format
The CRYOSTAT 2 Team comprises of experts in Trauma, Haematology, Emergency Medicine and clinical trial support staff.
The Lead for the London Major Trauma System, Professor of Trauma Sciences at the Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, UK.
Consultant Haematologist for the National Health Service Blood & Transplant at the John Radcliffe Hospital, Oxford, UK.
Consultant Trauma & Vascular Surgeon and Clinical Lecturer for the Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, UK.
Consultant Haematologist for the Oxford Haemophilia & Thrombosis Centre, Oxford University Hospitals Trust.
Consultant in Haemostasis and Transfusion Medicine NHSBT and Barts Health NHS Trust, UK.
Consultant in Emergency Medicine, University Hospitals Bristol NHS Foundation Trust, and Professor of Emergency Care, University of the West of England, Bristol.
Head of Clinical Operations NHSBT Clinical Trials Unit based in Cambridge, UK.
Clinical Operations Manager for the NHSBT Clinical Trials Unit based in Cambridge, UK
Clinical Trial Manager for the NHSBT Clinical Trials Unit based in Cambridge, UK
Trial Coordinator for the NHSBT Clinical Trials Unit based in Cambridge, UK.
This position of Trauma Operations Manager is currently vacant
Helen Thomas is Head of Clinical Trial Statistics for the NHSBT Clinical Trials Unit based in Bristol, UK.
Data Manager for the NHSBT Clinical Trials Unit based in Cambridge, UK.
Renate is a Senior Data Manager for the NHSBT Clinical Trials Unit based in Cambridge, UK