Clinical trial NCT04521881: Clinical Randomisation of an Anti-fibrinolytic in Symptomatic Mild Head Injury in Older Adults
Official title: Intramuscular Tranexamic Acid for the Treatment of Symptomatic Mild Traumatic Brain Injury in Older Adults: a Randomised, Double-blind, Placebo-controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Traumatic Brain Injury
Keywords: Traumatic brain injury, tranexamic acid, older adults
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
First posted: 2020-08-21
Enrollment: 10000
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomised, double blind, placebo controlled trial among 10,000 older adults with mild traumatic brain injury.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Emergency department discharge
timeFrame: within 24 hours
Secondary outcomes:
measure: Intracranial bleeding on CT scan
timeFrame: within 48 hours
measure: Head injury related death
timeFrame: within 48 hours
measure: All cause mortality
timeFrame: within 28 days
measure: Disability
timeFrame: within 28 days
measure: Global assessment of ability to self-care
timeFrame: within 28 days
measure: Neurosurgery
timeFrame: within 28 days
measure: Days in ICU
timeFrame: within 28 days
measure: Re-admission to hospital
timeFrame: within 28 days
measure: Vascular occlusive events
timeFrame: within 28 days
measure: Seizures
timeFrame: within 28 days
measure: Intramuscular injection site reaction
timeFrame: within 28 days
measure: Pneumonia
timeFrame: within 28 days
measure: Adverse events
timeFrame: within 28 days
measure: Dementia
timeFrame: 1 year
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: The Royal London Hospital
city: London
country: United Kingdom
facility: St George's Hospital
Study officials:
affiliation: London School of Hygiene and Tropical Medicine
name: Haleema Shakur-Still
role: STUDY_CHAIR
affiliation: London School of Hygiene and Tropical Medicine
name: Ian Roberts
role: STUDY_CHAIR
References: