Clinical Randomisation of an Anti-fibrinolytic in Symptomatic Mild Head Injury in Older Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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Intramuscular Tranexamic Acid for the Treatment of Symptomatic Mild Traumatic Brain Injury in Older Adults: a Randomised, Double-blind, Placebo-controlled Trial

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Drug: Tranexamic Acid 500 MG


Participation Criteria
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Eligibility Criteria
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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: has or had any impaired consciousness (loss of consciousness, amnesia, or confusion) 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)

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomised, double blind, placebo controlled trial among 10,000 older adults with mild traumatic brain injury.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>A single dose of Tranexamic acid 500mg given by intramuscular injection | Drug: Tranexamic Acid 500 MG<br>* given once as an intramuscular injection<br>|
| Placebo Comparator: Placebo<br>One Injection of the placebo which is 10 mL Sodium Chloride (0.9%) | Drug: Tranexamic Acid 500 MG<br>* given once as an intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Emergency department discharge | discharge | within 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intracranial bleeding on CT scan | any bleeding on the last scan conducted within 48 hours of randomisation | within 48 hours | 
| Head injury related death | In-hospital head injury-related death within 48 hours of injury | within 48 hours | 
| All cause mortality | Cause of death will be described | within 28 days | 
| Disability | The Barthel scale will be used to assess functional disability | within 28 days | 
| Global assessment of ability to self-care | Scale of 1 to 5 | within 28 days | 
| Neurosurgery | receipt of neurosurgery and type | within 28 days | 
| Days in ICU | Number of days | within 28 days | 
| Re-admission to hospital | readmission after discharge | within 28 days | 
| Vascular occlusive events | pulmonary embolism, myocardial infarction, deep vein thrombosis and stroke | within 28 days | 
| Seizures |  | within 28 days | 
| Intramuscular injection site reaction | frequency and type of reactions | within 28 days | 
| Pneumonia |  | within 28 days | 
| Adverse events | Any untoward medical occurrence (other than pre-specified outcomes) | within 28 days | 
| Dementia | 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. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Traumatic brain injury, tranexamic acid, older adults