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:
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.
Tom is a Trauma Operations Manager for the Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, UK
Claire is a Clinical Trial Coordinator for the Centre for Trauma Sciences, Blizard Institute, Queen Mary University of London, UK.
Helen Thomas is a Principal Statistician for the NHSBT Clinical Trials Unit based in Bristol, UK.
Renate is a Senior Data Manager for the NHSBT Clinical Trials Unit based in Cambridge, UK
Data Manager for the NHSBT Clinical Trials Unit based in Cambridge, UK.