The CRASH-3 Trial: Tranexamic acid for the treatment of significant traumatic brain injury.

Lead Research Organisation: London Sch of Hygiene and Trop Medicine
Department Name: Epidemiology and Population Health

Abstract

There are more deaths each year from injuries than from HIV, TB and malaria combined. Worldwide, about ten million people are killed or hospitalised because of a head injury every year. Most head injuries are caused by road traffic crashes, and because car use is increasing, the number of people suffering a head injury is increasing. Amongst those who survive a head injury, many are left severely disabled for the rest of their lives. For example, there is a high likelihood that Michael Schumacher will be permanently disabled as a result of his recent head injury. Most victims of head injury are young adults living in low and middle income countries. Because many of the victims are also breadwinners for their families, head injuries can also result in loss of income which, along with medical costs, can increase household debt and lead to a fall in living standards for the whole family. When the head is injured there is often bleeding inside the brain, which can continue for some time and worsen after hospital admission. This bleeding increases pressure inside the skull causing further damage to the brain, which can be fatal or result in serious disability for the patient. We think that we can prevent some of these deaths and disability by reducing the amount of bleeding in the brain after head injury. Tranexamic acid is a cheap drug that reduces bleeding in other conditions. A large trial in accident victims (other than those with head injury) found that it reduces the chances of bleeding to death. If this drug also works in patients with head injury and bleeding into the brain, this would be important to know because it could save lives at a very low cost.

We have already done two preparatory studies to see if tranexamic acid can help people who have bleeding inside the brain because of a head injury. Together, the results of the studies suggest that tranexamic acid should reduce the amount of bleeding inside the brain and could reduce their chances of dying or being disabled. However, because these studies were small, we are not very certain about the accuracy of their results. Also, they were not designed to find out whether tranexamic acid reduces disability. Because doctors are still unsure about whether tranexamic acid works, it is not given to patients with traumatic brain injury. But if a new clinical trial showed that it worked, this would change very quickly. We want to find out if tranexamic acid saves lives and reduces disability in people with traumatic brain injury.

We plan to study 10,000 patients with traumatic brain injury in countries throughout the world. We will give half of them tranexamic acid and the other half a dummy medicine called a placebo. To make sure that the two groups are the same apart from tranexamic acid, we will decide who gets tranexamic acid and who gets placebo using the modern equivalent of the toss of a coin (this is called randomisation). Everyone will of course get all the treatments that doctors usually give to traumatically brain injured patients. At the end of the trial we will see if giving tranexamic acid on top of all the usual treatments improves survival and other patient outcomes. The study will be carried out by a team of researchers with lots of experience in doing clinical trials. In fact, it will be the same team that did the successful study of tranexamic acid in accident victims. The trial will cost several million pounds but if it shows (as we hope it will) that tranexamic acid works, we will have a very cheap way of reducing the number of people who die and are disabled after a head injury. The start up phase of trial is underway and over a thousand patients have been recruited. The trial procedures work well. This application is for funds to continue recruitment to 10,000 patients.

Technical Summary

The CRASH-3 trial is a multi-centre, randomised placebo controlled trial of the effects of the early administration (within 8 hours of injury) of tranexamic acid on death, disability and vascular occlusive events in patients with acute traumatic brain injury. A total of 10,000 adult TBI patients who fulfil the eligibility criteria will be randomised to receive either TXA or matching placebo. All adults with TBI who are within eight hours of injury, with any intracranial bleeding on CT scan or who have a Glasgow Coma Score (GCS) of 12 or less, and do not require immediate blood transfusion for extra-cranial bleeding, will be eligible for inclusion. The main criterion is the doctor's 'uncertainty' as to whether or not to use TXA in a particular patient. This pragmatic approach allows us to see whether TXA works in real-life conditions.

The primary outcome is death in hospital within one month of injury (cause of death will be described). Secondary outcomes are disability and other patient orientated outcomes; vascular occlusive events (myocardial infarction, pulmonary embolism, deep vein thrombosis); stroke; seizures; neurosurgical intervention and days in intensive care.

We are working with an established network of hospitals that has successfully delivered many global trauma trials (CRASH-1 and CRASH-2 trials). Nigeria and Pakistan were major contributors to these trials and a research partnership has been established with them to help co-ordinate the CRASH-3 trial. LSHTM will build clinical trials research capacity in these settings by providing oversight, training and guidance in conducting clinical trials to the highest global standards.

Planned Impact

The main beneficiaries of the results of the CRASH-3 trial will be trauma patients and their families in low and middle income countries where the burden of TBI is greatest. Traumatic brain injury mostly affects economically active young adults and many will experience permanent disability. Michael Schumacher is a well known example of someone in the prime of life who might well be permanently disabled as a result of intracranial bleeding following a TBI. However, in low and middle income countries traumatic brain injury is an important cause of family poverty. Many households are made destitute when a family member sustains a traumatic brain injury. Medical costs and the loss of income can lead to decreased food consumption, a fall in living standards and increased indebtedness.

With growing motorisation, the incidence of traumatic brain injury is increasing rapidly in low and middle income countries. There are now more deaths from traumatic brain injury each year than from HIV. Tranexamic acid is inexpensive and simple to administer and, if shown to be effective in the treatment of traumatic brain injury, is likely to be highly cost effective. It is widely available in generic form in most countries. On the basis of the results of the CRASH-2 trial, tranexamic acid was included on the World Health Organization list of essential medicines which should further increase its availability in low and middle income countries. Tranexamic acid is potentially a simple, inexpensive, widely practicable treatment for a common cause of mortality and morbidity in low and middle income countries. If shown to be effective as a treatment for traumatic brain injury it could be rapidly implemented in global clinical practice.

Civilians and soldiers injured in conflict situations are also potential research beneficiaries. The use of improvised explosive devices in Afghanistan and Iraq has resulted in large increases in blast injuries to the brain. These cause significant mortality and disability in both civilian and military personnel. Although tranexamic acid is not a patented medicine, the findings from this trial could have important implications for new drug discovery. The results of the CRASH-2 trial have already stimulated many studies to understand the physiological role of plasmin in fibrinolysis and inflammation and could stimulate the development of new anti-plasmin medications.

If tranexamic acid is shown to be safe and effective as a treatment of traumatic intracranial bleeding it would almost certainly have implications for the management of haemorrhagic stroke, which is a major cause of death and disability worldwide. Our research team is already working with stroke researchers and a clinical trial of tranexamic acid in stroke is now underway.

Publications

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Ker K (2016) Does tranexamic acid prevent postpartum haemorrhage? A systematic review of randomised controlled trials. in BJOG : an international journal of obstetrics and gynaecology

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Mahmood A (2016) Does tranexamic acid improve outcomes in traumatic brain injury? in BMJ (Clinical research ed.)

 
Title CRASH-3 Trial - Ian Roberts presents at the World Congress on Intensive Care in Melbourne - 
Description - The first release of the CRASH-3 Trial results. Prof Ian Roberts (Chief Investigator) explains the significance of the results at the World Congress on Intensive Care in Melbourne. https://www.youtube.com/watch?v=3KD6vZRJN5k 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Title CRASH-3 Trial - Professor Ian Roberts presents the final results 
Description Video of Ian presenting to Malaysia collaborators. https://www.youtube.com/watch?v=_a-fIxqGkTc 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Title CRASH-3 poem 
Description A poem expressing the importance of randomising and treating patients as early as possible to prevent further brain damage. 
Type Of Art Film/Video/Animation 
Year Produced 2016 
Impact This video was circulated to CRASH-3 collaborators worldwide to help raise awareness of the importance of early randomisation in the trial 
 
Title CRASH-3 trial film 
Description Film featuring the co-lead of the study, a trauma neurosurgeon, and patient who was involved in the study explaining the trial results and why they are so important. http://bit.ly/CRASH3Trial 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Title CRASH-3 trial trailer 
Description A shorter version of the CRASH-3 film featuring Prof Ian Roberts and Pam Foley, a participant from the trial. https://www.dropbox.com/sh/n91fjmf0loggc7e/AABKkivUvXf_9vY4IMRiXqwVa?dl=0 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Title Film production 
Description A short film to show the biological mechanism of action of tranexamic acid. This includes: the Script & Character, Environment Designs and the Animatic as part of the delivery. 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact to identify how the biological mechanism of action of tranexamic acid can impact on the urgent treatment of bleeding. 
 
Title Pam's Story 
Description A video of Pam Foley, a CRASH-3 trial participant, explaining her experience of traumatic brain injury and the effect it's had on her life. http://bit.ly/CRASH3Pam 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Title Social media results explainer video 
Description A short film breaking down the key points from the press release as a slideshow. https://www.dropbox.com/sh/n91fjmf0loggc7e/AABKkivUvXf_9vY4IMRiXqwVa?dl=0 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Title TXA animation 
Description Animation explaining the mechanism of action of TXA through metaphor canines. http://bit.ly/TXAFilm 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Title • CRASH-3 trial animation 
Description Animation explaining the mechanism of action of TXA through metaphor canines. http://bit.ly/TXAFilm 
Type Of Art Film/Video/Animation 
Year Produced 2019 
Impact The CRASH-3 trial, the largest clinical trial in head injury ever conducted, has found that tranexamic acid, a low cost and widely available drug, reduces head injury death by up to 20% depending on the severity of the injury. The CRASH-3 trial is the first study to identify a safe and effective neuroprotective drug for traumatic brain injury. Bearing in mind that traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year, this is a major medical discovery. 
 
Description After 7 years of international collaboration, we are delighted to be sharing with you the CRASH-3 trial results.

The CRASH-3 trial is the first evidence of a drug which can prevent death following Traumatic Brain Injury (TBI). Tranexamic Acid (TXA) is a safe, low cost, and widely available drug which could prevent deaths from TBI by as much as 20% depending on severity of the injury.

Listen below to hear more about CRASH-3 and how TXA could be a potentially life-saving treatment. Pam Foley suffered a TBI after falling off her bike and was asked to participate in the CRASH-3 trial - hear her story below.

Please refer to the below link:
https://crash3.lshtm.ac.uk/blog/crash-3-trial-results/
Exploitation Route Our results show that tranexamic acid is safe in patients with TBI and that treatment within 3 h of injury reduces head injury-related death. Patients should be treated as soon as possible after injury.
This study represents an enormous effort in studying a difficult clinical problem. Considering the results of CRASH-3 with those of CRASH-212 (20 211 patients with trauma) and WOMAN13 (20 060 patients with peripartum haemorrhage), more than 53 000 patients have been randomly assigned in the study of tranexamic acid and the drug's effects on patients with bleeding. The results of each study independently and together are clear: tranexamic acid reduces risk of death due to bleeding, regardless of the cause.

Furthermore, tranexamic acid must be given early-within 3 h of bleeding onset-to be effective. These data suggest a fundamental truth regarding the pathophysiology of life-threatening haemorrhage-namely, that early activation of the fibrinolytic protease cascade is intimately linked to poor outcomes in patients with bleeding, perhaps because of various mechanisms,15 including worsened bleeding due to clot breakdown, activation of inflammatory pathways, and increased endothelial permeability leading to tissue, especially brain, oedema. Tranexamic acid offers a means to mitigate this maladaptive response to injury.

CRASH-3 is the first trial of a pharmacological intervention applied in the acute setting to show improved outcomes in patients with TBI. The use of 28-day head injury-related mortality as the primary endpoint probably biased the treatment effect towards the null because tranexamic acid is most likely to benefit patients with TBI with intracranial bleeding at risk of early mortality, whereas late deaths are unlikely to be affected by tranexamic acid. Indeed, the authors report that the greatest reduction in head injury-related deaths occurred in the first 24 h after injury in a manner consistent with that observed in CRASH-2. Future studies of tranexamic acid or other haemostatic interventions should reflect what is physiologically plausible and focus on endpoints of early bleeding-related death that clearly link intervention to outcome.
Sectors Healthcare,Other

 
Description Health Technology Assessment
Amount £123,434,075 (GBP)
Funding ID 14/190/01 
Organisation National Institute for Health Research 
Department Health Technology Assessment Programme (HTA)
Sector Public
Country United Kingdom
Start 10/2014 
End 01/2020
 
Description JP Moulton Charitable Foundation
Amount £50,500 (GBP)
Organisation J P Moulton Charitable Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2012 
End 12/2015
 
Description Pharmacokinetics of intramuscular tranexamic acid in trauma patients: a clinical trial
Amount £236,999 (GBP)
Organisation J P Moulton Charitable Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2019 
End 10/2020
 
Description The effect of Intramuscular TXA on death, disability and dementia on older adults with mild traumatic brain injury
Amount £717,728 (GBP)
Organisation J P Moulton Charitable Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2020 
End 11/2021
 
Title FREEBIRD 
Description Free data sharing website 
Type Of Material Improvements to research infrastructure 
Year Produced 2012 
Provided To Others? Yes  
Impact Research data provided for student projects and external investigators. 
URL http://freebird.lshtm.ac.uk/
 
Description Our collaborators and partners constitute of Coordinating Centres in Pakistan and Nigeria, and other UK collaborations. 
Organisation Barts Health NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Collaborator Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Impact Thanks to our collaborations we have built an amazing network of collaborators here at LSHTM and in over 50 countries worldwide. Our interest is to design and conduct clinical trials that allow for critically ill patients to benefit for scientific advances. Additionally, our interest lies in developing novel ways of communicating the work we do to clinicians, policy makers and the wider public to make sure patients benefit from the results of our research. Thanks to these impressive collaborations, we were able to change clinical practice as per the examples below: Woman Trial: WHO updates recommendation on intravenous tranexamic acid for the treatment of postpartum haemorrhage National Institute for Health and Care excellence (NICE), has referred to the following in their guidance and advice: CRASH-2 Trial: Significant haemorrhage following trauma: tranexamic acid Evidence summary [ESUOM1]Published date: October 2012 CRASH-3: Major trauma: service delivery NICE guideline [NG40] Published date: February 2016
Start Year 2010
 
Description Our collaborators and partners constitute of Coordinating Centres in Pakistan and Nigeria, and other UK collaborations. 
Organisation Rawalpindi Medical College
Country Pakistan 
Sector Hospitals 
PI Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Collaborator Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Impact Thanks to our collaborations we have built an amazing network of collaborators here at LSHTM and in over 50 countries worldwide. Our interest is to design and conduct clinical trials that allow for critically ill patients to benefit for scientific advances. Additionally, our interest lies in developing novel ways of communicating the work we do to clinicians, policy makers and the wider public to make sure patients benefit from the results of our research. Thanks to these impressive collaborations, we were able to change clinical practice as per the examples below: Woman Trial: WHO updates recommendation on intravenous tranexamic acid for the treatment of postpartum haemorrhage National Institute for Health and Care excellence (NICE), has referred to the following in their guidance and advice: CRASH-2 Trial: Significant haemorrhage following trauma: tranexamic acid Evidence summary [ESUOM1]Published date: October 2012 CRASH-3: Major trauma: service delivery NICE guideline [NG40] Published date: February 2016
Start Year 2010
 
Description Our collaborators and partners constitute of Coordinating Centres in Pakistan and Nigeria, and other UK collaborations. 
Organisation University College Hospital, Ibadan
Country Nigeria 
Sector Hospitals 
PI Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Collaborator Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Impact Thanks to our collaborations we have built an amazing network of collaborators here at LSHTM and in over 50 countries worldwide. Our interest is to design and conduct clinical trials that allow for critically ill patients to benefit for scientific advances. Additionally, our interest lies in developing novel ways of communicating the work we do to clinicians, policy makers and the wider public to make sure patients benefit from the results of our research. Thanks to these impressive collaborations, we were able to change clinical practice as per the examples below: Woman Trial: WHO updates recommendation on intravenous tranexamic acid for the treatment of postpartum haemorrhage National Institute for Health and Care excellence (NICE), has referred to the following in their guidance and advice: CRASH-2 Trial: Significant haemorrhage following trauma: tranexamic acid Evidence summary [ESUOM1]Published date: October 2012 CRASH-3: Major trauma: service delivery NICE guideline [NG40] Published date: February 2016
Start Year 2010
 
Description Our collaborators and partners constitute of Coordinating Centres in Pakistan and Nigeria, and other UK collaborations. 
Organisation University of Leicester
Country United Kingdom 
Sector Academic/University 
PI Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Collaborator Contribution We work within an international partnership of clinicians and scientists to obtain reliable answer to important questions. Acute severe bleeding is a leading cause of death everywhere. Our partnership uses long-term institutional relationships (MOUs in place) to tackle a shared research agenda. The diversity of knowledge and skills within the partnership is its strength. We strive to redress evidence hierarchies. Partnership research is published by the entire collaborative group with all contributors and their roles listed. The writing committee reflects scientific contribution and includes many more authors from LMICs than from HICs. We share opportunities to discuss the results in the mass media and to present at conferences and policy. The trial results are open access and all partners have access to the trial data via our data-sharing website. In this study, interdisciplinary collaboration is key and we draw on biostatistics, epidemiology, management, marketing, midwifery, obstetrics, paediatrics, pharmacology and psychology to answer the research question. We believe that global trials build clinical trial capacity in all countries regardless of income level and have shown that international collaboration can generate globally applicable new knowledge. Large trials to identify the effects on mortality of widely practicable treatments for common conditions can use simple protocols and do not need elaborate infrastructure. By focusing on scientific principles and avoiding overly bureaucratic processes, we can assure data quality regardless of income level. Exposing a diversity of professionals (doctors, midwives, nurses, and administrators) to clinical trial research can change hospital cultures and creating a network of recruiting hospitals builds a cadre of experienced trialists."
Impact Thanks to our collaborations we have built an amazing network of collaborators here at LSHTM and in over 50 countries worldwide. Our interest is to design and conduct clinical trials that allow for critically ill patients to benefit for scientific advances. Additionally, our interest lies in developing novel ways of communicating the work we do to clinicians, policy makers and the wider public to make sure patients benefit from the results of our research. Thanks to these impressive collaborations, we were able to change clinical practice as per the examples below: Woman Trial: WHO updates recommendation on intravenous tranexamic acid for the treatment of postpartum haemorrhage National Institute for Health and Care excellence (NICE), has referred to the following in their guidance and advice: CRASH-2 Trial: Significant haemorrhage following trauma: tranexamic acid Evidence summary [ESUOM1]Published date: October 2012 CRASH-3: Major trauma: service delivery NICE guideline [NG40] Published date: February 2016
Start Year 2010
 
Description CRASH-3 Clinical Trial Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Meeting was held with collaborators from all over Pakistan on 18th April 2018 in Lahore.
The purpose is to:
share experiences of the trial organisation and conduct.
develop a strong, committed team of collaborators
update the Pakistan team on the trial progress globally and in Pakistan
discuss trial related issues encountered by the collaborators and identify solutions
create an action plan for Halt-It's final year for Pakistan
Year(s) Of Engagement Activity 2018
 
Description CRASH-3 MALAYSIA COLLABORATORS RESULTS MEETING 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The meeting was held on 10th Oct 2019.

Its purpose:
* CRC Role in CRASH 3 trial and research in Malaysia
* The CRASH-3 trial a global international effort
* The CRASH-3 trial results
* Intracranial bleeding in TBI - baseline CT scan data
* What do the trial results mean for clinical practice?
* What do the trial results mean for clinical research?
* Where do we go from here?
Year(s) Of Engagement Activity 2019
 
Description CRASH-3 National meeting in Japan 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Meeting to bring together CRASH-3 trial collaborators in Japan and to provide an update on the trial progress
Year(s) Of Engagement Activity 2015
 
Description CRASH-3 National meeting in Malaysia 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Meeting to bring together CRASH-3 trial collaborators in Malaysia and to provide an update on the trial progress
Year(s) Of Engagement Activity 2015,2016
 
Description CRASH-3 National meeting in Pakistan 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Meeting to bring together CRASH-3 trial collaborators in Pakistan and to provide an update on the trial progress
Year(s) Of Engagement Activity 2016,2017
 
Description CRASH-3 National meeting in Pakistan 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Meeting to bring together CRASH-3 trial collaborators in Pakistan and to provide an update on the trial progress
Year(s) Of Engagement Activity 2015
 
Description CRASH-3 Pakistan Collaborators Results Meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact The meeting was held on 16th Sept 2019.
Its purpose:

• Present the CRASH-3 trial results.
• Examine the implications of the results for clinical practice.
• Discuss the implications of the results for future research.
Year(s) Of Engagement Activity 2019
 
Description CRASH-3 UK Collaborators Results Meeting 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact The meeting was held on 6th Sept 2019.
Its purpose was:

• Present the CRASH-3 trial results.
• Examine the implications of the results for clinical practice.
• Discuss the implications of the results for future research
Year(s) Of Engagement Activity 2019
 
Description Invited Lecture: Advances in Haematology Course, Imperial College London, 2019. 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Invited Lecture: Advances in Haematology Course, Imperial College London, 2019.
Year(s) Of Engagement Activity 2019
 
Description Invited Lecture: Japanese Society of Intensive Care (Kyoto, 2019) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Lecture: Japanese Society of Intensive Care (Kyoto, 2019).
Year(s) Of Engagement Activity 2014,2019
 
Description Invited Lecture: SFAR (Paris 2019). Tranexamic acid in bleeding 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited Lecture: SFAR (Paris 2019). Tranexamic acid in bleeding
Year(s) Of Engagement Activity 2019
 
Description Keynote Lecture: International Society of Thrombosis and Haemostasis, Melbourne 2019.Keynote Lecture: The British Society for Haematology (Glasgow, 2019) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Keynote Lecture: International Society of Thrombosis and Haemostasis, Melbourne 2019.Keynote Lecture: The British Society for Haematology (Glasgow, 2019)
Year(s) Of Engagement Activity 2019
 
Description Keynote Lecture: Royal College of Emergency Medicine (Gateshead 2019) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Keynote Lecture: Royal College of Emergency Medicine (Gateshead 2019)
Year(s) Of Engagement Activity 2019
 
Description Numerous presentations on the CRASH-2, CRASH-3 and HALT-IT clinical trials 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Better implementation of results of trials already completed, and better recruitment to ongoing trials.
Year(s) Of Engagement Activity 2014
 
Description Plenary Lecture: World Congress on Intensive Care, Melbourne 2019. The CRASH-3 trial results. Keynote Lecture: International Society of Thrombosis and Haemostasis, Melbourne 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Plenary Lecture: World Congress on Intensive Care, Melbourne 2019.
The CRASH-3 trial results. Keynote Lecture: International Society of Thrombosis and Haemostasis, Melbourne 2019
Year(s) Of Engagement Activity 2019