Traumatic Brain InjuryPhase 3CRASH-4NCT04521881
Clinical Randomisation of an Anti-fibrinolytic in Symptomatic Mild Head Injury in Older Adults
A Phase 3 study testing Tranexamic Acid 500 MG in people with Traumatic Brain Injury, run by London School of Hygiene and Tropical Medicine at 2 sites in United Kingdom.
Trial 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 Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- Tranexamic Acid 500 MG
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5,000 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 18 Apr 2021to 31 Jan 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- TXA not clearly indicated (e.g. major bleeding) or contraindicated (e.g. suspected stroke)
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom2 sites, 2 recruiting
- Recruiting
The Royal London Hospital
London, London, E1 1FR
Ben Bloom
- Recruiting
St George's Hospital
London, London, SW17 0QT
Heather Jarman
About this study
Official title: Intramuscular Tranexamic Acid for the Treatment of Symptomatic Mild Traumatic Brain Injury in Older Adults: a Randomised, Double-blind, Placebo-controlled Trial
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
Read the 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.
- Conditions
- Traumatic Brain Injury
- Being tested
- Tranexamic Acid 500 MG
- Keywords
- Traumatic brain injury, tranexamic acid, older adults
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic Acid 500 MGDrug
given once as an intramuscular injection
| Study group | Role | What they receive |
|---|---|---|
| Active | Active comparator | A single dose of Tranexamic acid 500mg given by intramuscular injection Receives: Drug: Tranexamic Acid 500 MG |
| Placebo | Placebo comparator | One Injection of the placebo which is 10 mL Sodium Chloride (0.9%) Receives: Drug: Tranexamic Acid 500 MG |
What is being measured
The primary outcome is the main question the study is designed to answer.
Emergency department discharge
discharge
Measured: within 24 hours
Secondary outcomes (15)
Intracranial bleeding on CT scan
any bleeding on the last scan conducted within 48 hours of randomisation
Measured: within 48 hours
Head injury related death
In-hospital head injury-related death within 48 hours of injury
Measured: within 48 hours
All cause mortality
Cause of death will be described
Measured: within 28 days
Disability
The Barthel scale will be used to assess functional disability
Measured: within 28 days
Global assessment of ability to self-care
Scale of 1 to 5
Measured: within 28 days
Neurosurgery
receipt of neurosurgery and type
Measured: within 28 days
Days in ICU
Number of days
Measured: within 28 days
Re-admission to hospital
readmission after discharge
Measured: within 28 days
Vascular occlusive events
pulmonary embolism, myocardial infarction, deep vein thrombosis and stroke
Measured: within 28 days
Seizures
Measured: within 28 days
Intramuscular injection site reaction
frequency and type of reactions
Measured: within 28 days
Pneumonia
Measured: within 28 days
Adverse events
Any untoward medical occurrence (other than pre-specified outcomes)
Measured: 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.
Measured: 1 year
Key TBI associated outcomes at 1 year
Incidence of Mood disorders, intracranial bleeding and convulsions
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Aug 2020
- Study start18 Apr 2021
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Jan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomised, double blind, placebo controlled trial among 10,000 older adults with mild traumatic brain injury.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London School of Hygiene and Tropical Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Haleema Shakur-Still, Study chair, London School of Hygiene and Tropical MedicineIan Roberts, Study chair, London School of Hygiene and Tropical Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04521881
- Sponsor's protocol ID
- 2020-KEP-456
- Other IDs
- 2020-003391-40
- Acronym
- CRASH-4
- Status last verified
- Mar 2026
- First submitted
- 18 Aug 2020
- Last updated
- 12 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be shared publicly when all planned analyses are completed by the CRASH-4 Trial Collaborators. This will be hosted on freebird.lshtm.ac.uk
Study at a glance
From the registry record, last updated by the sponsor on 12 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intramuscular Tranexamic Acid for the Treatment of Symptomatic Mild Traumatic Brain Injury in Older Adults: a Randomised, Double-blind, Placebo-controlled Trial
- ClinicalTrials.gov ID
- NCT04521881
- Acronym / sponsor ID
- CRASH-4 / 2020-KEP-456
- Conditions
- Traumatic Brain Injury
- Keywords
- Traumatic brain injury, tranexamic acid, older adults
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 5,000 participants (estimated)
- Lead sponsor
- London School of Hygiene and Tropical MedicineUniversity, hospital or other
- Study start
- 18 Apr 2021 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Jan 2028 (estimated)
- First posted
- 21 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomised, double blind, placebo controlled trial among 10,000 older adults with mild traumatic brain injury.
| Arm | Type | Receives |
|---|---|---|
| Active | Active comparator | Drug: Tranexamic Acid 500 MGA single dose of Tranexamic acid 500mg given by intramuscular injection |
| Placebo | Placebo comparator | Drug: Tranexamic Acid 500 MGOne Injection of the placebo which is 10 mL Sodium Chloride (0.9%) |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:
- 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)
Key exclusion criteria (1 listed)
- TXA not clearly indicated (e.g. major bleeding) or contraindicated (e.g. suspected stroke)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic Acid 500 MGgiven once as an intramuscular injection | Drug | Active, Placebo |
Primary outcome
Emergency department discharge
Time frame: within 24 hours
discharge
15 secondary outcomes
Intracranial bleeding on CT scan
Time frame: within 48 hours
Head injury related death
Time frame: within 48 hours
All cause mortality
Time frame: within 28 days
Disability
Time frame: within 28 days
Global assessment of ability to self-care
Time frame: within 28 days
Neurosurgery
Time frame: within 28 days
Days in ICU
Time frame: within 28 days
Re-admission to hospital
Time frame: within 28 days
Vascular occlusive events
Time frame: within 28 days
Seizures
Time frame: within 28 days
Intramuscular injection site reaction
Time frame: within 28 days
Pneumonia
Time frame: within 28 days
Adverse events
Time frame: within 28 days
Dementia
Time frame: 1 year
Key TBI associated outcomes at 1 year
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Mar 2026.
- Trial websiteLink provided by the sponsor.
- TXA background informationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data will be shared publicly when all planned analyses are completed by the CRASH-4 Trial Collaborators. This will be hosted on freebird.lshtm.ac.uk
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Haleema Shakur-Still study chair
London School of Hygiene and Tropical Medicine
Ian Roberts study chair
London School of Hygiene and Tropical Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tranexamic Acid 500 MG in people with Traumatic Brain Injury, run by London School of Hygiene and Tropical Medicine at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Haleema Shakur-Still (+4407714139500, Haleema.Shakur@lshtm.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Emergency department discharge (time frame: within 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2026.