Global trial is first clear evidence that widely available drug reduces head injury deaths

October 15, 2019

A low cost and widely available drug could reduce deaths in traumatic brain injury patients by as much as 20%, depending on the severity of injury, according to a major study published in The Lancet. [1] The researchers say that tranexamic acid (TXA), a drug that prevents bleeding into the brain by inhibiting blood clot breakdown, has the potential to save hundreds of thousands of lives.

Led by the London School of Hygiene & Tropical Medicine, the global randomised trial included more than 12,000 head injury patients who were given either intravenous tranexamic acid or a placebo. [2] It found that administration of TXA within three hours of injury reduced the number of deaths. This effect was greatest in patients with mild and moderate traumatic brain injury (20% reduction in deaths), while no clear benefit was seen in the most severely injured patients. The trial found no evidence of adverse effects and there was no increase in disability in survivors when the drug was used. [3,4,5]

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year. [6] The CRASH-3 (Clinical Randomisation of an Antifbrinolytic in Significant Head Injury) trial is one of the largest clinical trials ever conducted into head injury. Patients were recruited from 175 hospitals across 29 countries.

Bleeding in or around the brain due to tearing of blood vessels is a common complication of TBI and can lead to brain compression and death. Although patients with very severe head injuries are unlikely to benefit from tranexamic acid treatment because they often have extensive brain bleeding prior to hospital admission and treatment, the study found a substantial benefit in patients with less severe injuries who comprise the majority (over 90%) of TBI cases. [7]

Ian Roberts, Professor of Clinical Trials at the London School of Hygiene & Tropical Medicine, who co-led the study, said: "We already know that rapid administration of tranexamic acid can save lives in patients with life threatening bleeding in the chest or abdomen such as we often see in victims of traffic crashes, shootings or stabbings. This hugely exciting new result shows that early treatment with TXA also cuts deaths from head injury. It's an important breakthrough and the first neuroprotective drug for patients with head injury.

"Traumatic brain injury can happen to anyone at any time, whether it's through an incident like a car crash or simply falling down the stairs. We believe that if our findings are widely implemented they will boost the chances of people surviving head injuries in both high income and low income countries around the world."

Because TXA prevents bleeds from getting worse, but cannot undo damage already done, early treatment is critical. The trial data showed a 10% reduction in treatment effectiveness for every 20-minute delay, suggesting that patients should be treated with TXA as soon as possible after head injury. [8,9]

Antoni Belli, Neurosurgeon and Professor of Trauma Neurosurgery at the University of Birmingham and co-investigator for trial, said: "This is a landmark study. After decades of research and many unsuccessful attempts, this is the first ever clinical trial to show that a drug can reduce mortality after traumatic brain injury. Not only do we think this could save hundreds of thousands of lives worldwide, but it will no doubt renew the enthusiasm for drug discovery research for this devastating condition."

Dr Ben Bloom, Consultant in Emergency Medicine at Barts Health NHS Trust, the UK's largest recruiter into the trial with more than 500 patients enrolled, said: "Treating traumatic brain injury is extremely challenging with very few treatment options available for patients. Thanks to these latest results, which are applicable to patients with head injuries of any cause and of all demographics, clinicians now have a potentially powerful new treatment available to them."

The most common causes of TBI worldwide are road traffic crashes (which predominantly affect young adults) or falls (which are a major problem in older adults), and the incidence is increasing. In both cases, patients can experience permanent disability or death. Representatives from the charity that supports roach crash victims in the UK, Roadpeace, were involved in the design of the trial.

Amy Aeron-Thomas, Justice and Advocacy Manager from Roadpeace and co-author on the paper said: "It's always better to prevent road crashes in the first place, but these results show that if a crash can't be prevented, death can still be avoided. Given the time to treatment implications, it's more important than ever that the post-crash response is as efficient as possible."

CRASH-3 follows successful previous research involving 20,000 trauma patients, which showed that TXA reduced deaths due to bleeding outside of the skull by almost a third if given within three hours. Based on those trial results, tranexamic acid was included in guidelines for the pre-hospital care of trauma patients. However, patients with isolated traumatic brain injury were specifically excluded. [10]

The authors noted some limitations of the trial, including wide confidence intervals despite the large trial size, and the fact that more patients with un-survivable head injuries were included in the trial than anticipated, which diluted the treatment effect.
-end-
The trial was jointly funded by the Department for International Development (DFID), the Medical Research Council (MRC), the National Institute for Health Research (NIHR), (through the Department of Health and Social Care), and Wellcome. The early phase of the trial was funded was funded by The JP Moulton Charitable Foundation. [11]

Notes to EditorsThe London School of Hygiene & Tropical Medicine (LSHTM) is a world-leading centre for research, postgraduate studies and continuing education in public and global health. LSHTM has a strong international presence with 3,000 staff and 4,000 students working in the UK and countries around the world, and an annual research income of £140 million. LSHTM is one of the highest-rated research institutions in the UK, is partnered with two MRC University Units in The Gambia and Uganda, and was named University of the Year in the Times Higher Education Awards 2016. Our mission is to improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice. http://www.lshtm.ac.uk

The National Institute for Health Research (NIHR)

The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:The NIHR was established in 2006 to improve the health and wealth of the nation through research, and is funded by the Department of Health and Social Care. In addition to its national role, the NIHR commissions applied health research to benefit the poorest people in low- and middle-income countries, using Official Development Assistance funding. This work uses data provided by patients and collected by the NHS as part of their care and support and would not have been possible without access to this data. The NIHR recognises and values the role of patient data, securely accessed and stored, both in underpinning and leading to improvements in research and care. http://www.nihr.ac.uk/patientdata

London School of Hygiene & Tropical Medicine

Related Traumatic Brain Injury Articles from Brightsurf:

Point-of-care biomarker assay for traumatic brain injury
Intracranial abnormalities on CT scan in patients with traumatic brain injury (TBI) can be predicted by glial fibrillary acidic protein (GFAP) levels in the blood.

Long-studied protein could be a measure of traumatic brain injury
WRAIR scientists have recently demonstrated that cathepsin B, a well-studied protein important to brain development and function, can be used as biomarker, or indicator of severity, for TBI.

Reducing dangerous swelling in traumatic brain injury
After a traumatic brain injury (TBI), the most harmful damage is caused by secondary swelling of the brain compressed inside the skull.

Blue light can help heal mild traumatic brain injury
Daily exposure to blue wavelength light each morning helps to re-entrain the circadian rhythm so that people get better, more regular sleep which was translated into improvements in cognitive function, reduced daytime sleepiness and actual brain repair.

Dealing a therapeutic counterblow to traumatic brain injury
A team of NJIT biomedical engineers are developing a therapy which shows early indications it can protect neurons and stimulate the regrowth of blood vessels in damaged tissue.

Predictors of cognitive recovery following mild to severe traumatic brain injury
Researchers have shown that higher intelligence and younger age are predictors of greater cognitive recovery 2-5 years post-mild to severe traumatic brain injury (TBI).

Which car crashes cause traumatic brain injury?
Motor vehicle crashes are one of the most common causes of TBI-related emergency room visits, hospitalizations and deaths.

Traumatic brain injury and kids: New treatment guidelines issued
To help promote the highest standards of care, and improve the overall rates of survival and recovery following TBI, a panel of pediatric critical care, neurosurgery and other pediatric experts today issued the third edition of the Brain Trauma Foundation Guidelines for the Management of Pediatric Severe TBI.

Addressing sleep disorders after traumatic brain injury
Amsterdam, NL, December 10, 2018 - Disorders of sleep are some of the most common problems experienced by patients after traumatic brain injury (TBI).

Rutgers researchers discover possible cause for Alzheimer's and traumatic brain injury
Rutgers researchers discover a possible cause for Alzheimer's and traumatic brain injury, and the new mechanism may have also led to the discovery of an effective treatment.

Read More: Traumatic Brain Injury News and Traumatic Brain Injury Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.