Traumatic Brain Injury
Conditions
Keywords
Traumatic brain injury, tranexamic acid, older adults
Brief summary
Tranexamic acid (TXA) reduces head injury deaths. The CRASH-4 trial aims to assess the effects of early intramuscular TXA on intracranial haemorrhage, disability, death, and dementia in older adults with symptomatic mild head injury
Detailed description
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 (given intravenously) 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. CRASH-4 is a randomised, double blind, placebo-controlled trial in symptomatic mild TBI in about 10,000 older adults. The pilot phase will include about 500 patients. The 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.
Interventions
given once as an intramuscular injection
Sponsors
London School of Hygiene and Tropical Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Masking will be done by an independent clinical trials supply company. It will involve the removal of the original manufacturer's label and replacement with the clinical trial label bearing the randomisation number, which will be used as the pack identification. Apart from the randomisation number, all pack label texts will be identical for tranexamic acid and placebo.
Intervention model description
A randomised, double blind, placebo controlled trial among 10,000 older adults with mild traumatic brain injury.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 50 years or older (actual or estimated) * History or evidence of head injury (e.g. laceration, bruise, swelling or pain in head or face) * GCS ≥ 13 * Has one or more of the following: 1. has or had any impaired consciousness (loss of consciousness, amnesia, or confusion) 2. nausea or vomiting * Within 3 hours of injury (do not include if interval cannot be estimated e.g. patient unable to confirm time of fall or patient found on floor after an unwitnessed fall and home alone) * Not living in a nursing home, mental health institution or prison * Patient will be conveyed to or is admitted to a participating hospital
Exclusion criteria
\- TXA not clearly indicated (e.g. major bleeding) or contraindicated (e.g. suspected stroke)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Emergency department discharge | within 24 hours | discharge |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Intracranial bleeding on CT scan | within 48 hours | any bleeding on the last scan conducted within 48 hours of randomisation |
| Head injury related death | within 48 hours | In-hospital head injury-related death within 48 hours of injury |
| All cause mortality | within 28 days | Cause of death will be described |
| Disability | within 28 days | The Barthel scale will be used to assess functional disability |
| Global assessment of ability to self-care | within 28 days | Scale of 1 to 5 |
| Neurosurgery | within 28 days | receipt of neurosurgery and type |
| Days in ICU | within 28 days | Number of days |
| Re-admission to hospital | within 28 days | readmission after discharge |
| Vascular occlusive events | within 28 days | pulmonary embolism, myocardial infarction, deep vein thrombosis and stroke |
| Seizures | within 28 days | — |
| Intramuscular injection site reaction | within 28 days | frequency and type of reactions |
| Pneumonia | within 28 days | — |
| Adverse events | within 28 days | Any untoward medical occurrence (other than pre-specified outcomes) |
| Dementia | 1 year | The occurrence of all-cause dementia will be determined 12 months after randomisation. Dementia will be identified through linkage to routinely collected health-care data. |
| Key TBI associated outcomes at 1 year | 1 year | Incidence of Mood disorders, intracranial bleeding and convulsions |
Countries
United Kingdom
Contacts
CONTACTHaleema Shakur-Still
STUDY_CHAIRHaleema Shakur-Still
London School of Hygiene and Tropical Medicine
STUDY_CHAIRIan Roberts
London School of Hygiene and Tropical Medicine
Outcome results
None listed