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

A low cost and widely available drug could reduce deaths in traumatic brain injury patients by as much as 20 per cent depending on the severity of injury, according to a major study carried out in collaboration with the University of Birmingham.

The research, published in The Lancet, showed 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.

The global randomised trial included more than 12,000 head injury patients who were given either intravenous tranexamic acid or a placebo.

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.

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.

Traumatic brain injury (TBI) is a leading cause of death and disability worldwide with an estimated 69 million new cases each year. 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.

Co-investigator for trial Professor Tony Belli, of the University of Birmingham’s Institute of Inflammation and Ageing, 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.”

Ian Roberts, Professor of Clinical Trials at the London School of Hygiene & Tropical Medicine, who co-led the study, added: “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.

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.

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.

Notes to editors:

  • For more information please contact Emma McKinney, Communications Manager (Health Sciences), University of Birmingham, tel: +44 (0) 121 414 6681, or contact the press office on +44 (0) 7789 921 165.
  • The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.
  • Roberts et al (2019). ‘The CRASH-3 trial collaborators, Effects of tranexamic acid on death, disability, vascular occlusive events and other morbidities in patients with acute traumatic brain injury (CRASH-3): a randomised, placebo-controlled trial’. The Lancet. DOI: 10.1016/ S0140-6736(19)32233-0
  • The National Institute for Health Research (NIHR) is the nation's largest funder of health and care research. The NIHR:
  • Funds, supports and delivers high quality research that benefits the NHS, public health and social care
  • Engages and involves patients, carers and the public in order to improve the reach, quality and impact of research
  • Attracts, trains and supports the best researchers to tackle the complex health and care challenges of the future
  • Invests in world-class infrastructure and a skilled delivery workforce to translate discoveries into improved treatments and services
  • Partners with other public funders, charities and industry to maximise the value of research to patients and the economy
  • 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 supports applied health research for the direct and primary benefit of people in low- and middle-income countries, using UK aid from the UK government.