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

Phase 3

Recruiting

• Conditions: Traumatic Brain Injury
• Interventions: Drug: Tranexamic Acid 500 MG

• Registration Number: NCT04521881
• Lead Sponsor: London School of Hygiene and Tropical Medicine

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.

Study Timeline

• Study First Submitted: 2020-08-18
• Study First Submitted QC: 2020-08-18
• Study First Posted: 2020-08-21
• Study Start: 2021-04-18
• Status Verified: 2022-08
• Last Update Submitted: 2023-01-04
• Last Update Posted: 2023-01-05
• Primary Completion: 2024-03-31
• Study Completion: 2025-03-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 10000

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

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Exclusion Criteria

• TXA not clearly indicated (e.g. major bleeding) or contraindicated (e.g. suspected stroke)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active	Tranexamic Acid 500 MG	A single dose of Tranexamic acid 500mg given by intramuscular injection
Placebo	Tranexamic Acid 500 MG	One Injection of the placebo which is 10 mL Sodium Chloride (0.9%)

Primary Outcome Measures

Name	Time	Method
Emergency department discharge	within 24 hours	discharge

Secondary Outcome Measures

Name	Time	Method
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
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
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.

Trial Locations

Locations (2)

St George's Hospital; 🇬🇧 London, United Kingdom

The Royal London Hospital; 🇬🇧 London, United Kingdom