Clinical Randomisation of an Anti-fibrinolytic in Symptomatic Mild Head Injury in Older Adults
Trial Status: recruiting
Start Date: 01 April 2020
End Date: 30 November 2021
Participants recruited to date: 1
Trial protocol: V1.2, dated 19/01/2021
A fall from standing height in older adults is the commonest cause of major trauma in the UK. Traumatic brain injury (TBI) accounts for half of trauma admissions in older adults and is a leading cause of death and disability. Because the population aged over 70 years is increasing, the number of older adults with TBI will continue to rise. Most (90%) of the 1.4 million TBI patients seen each year in emergency departments in England and Wales have mild (Glasgow Coma Scale (GCS) score 13-15) head injury, but the term ‘mild’ is misleading in older adults who have higher death rates and worse outcomes than younger patients. Due to increased use of anticoagulant and antiplatelet drugs, older adults are more likely to suffer intracranial bleeding after mild TBI. TBI is also a strong risk factor for dementia in older adults.
Tranexamic acid (TXA) reduces bleeding by inhibiting the enzymatic breakdown of fibrin blood clots. Results from randomised trials (CRASH-3 and NCT01990768) show that early treatment with TXA reduces head injury deaths (pooled RR 0.89, 95% CI 0.80-0.99). In the CRASH-3 trial, the reduction in head injury deaths with TXA was largest in patients with mild and moderate head injuries, particularly if patients were treated soon after injury. However, the CRASH-3 trial included mild TBI patients only if they had intracranial bleeding on CT scan. It is uncertain whether the results apply to mild TBI patients more generally.
Intracranial bleeding occurs soon after injury and early treatment is most effective. We have shown that TXA is rapidly absorbed after intramuscular injection in trauma patients without local side effects. This means that paramedics can give intramuscular TXA before transport to hospital, and for those who do not travel by ambulance, intramuscular TXA can be given immediately on hospital arrival. If early intramuscular TXA treatment reduces death and disability in older adults with mild TBI this would be a major medical advance that would improve the care of many millions of patients in the UK and world-wide.
The CRASH-4 trial aims to provide reliable evidence about the effects of early intramuscular TXA on intracranial haemorrhage, disability, death, and dementia in older adults with symptomatic mild head injury.