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Clinical Randomisation of an Anti-fibrinolytic in Symptomatic Mild Head Injury in Older Adults (CRASH-4)

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ClinicalTrials.gov Identifier: NCT04521881
Recruitment Status : Recruiting
First Posted : August 21, 2020
Last Update Posted : January 5, 2023
Sponsor:
Information provided by (Responsible Party):
London School of Hygiene and Tropical Medicine

Study Description
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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

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Drug: Tranexamic Acid 500 MG Phase 3

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
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A randomised, double blind, placebo controlled trial among 10,000 older adults with mild traumatic brain injury.
Masking: Quadruple (Participant, Care Provider, 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.
Primary Purpose: Treatment
Official Title: Intramuscular Tranexamic Acid for the Treatment of Symptomatic Mild Traumatic Brain Injury in Older Adults: a Randomised, Double-blind, Placebo-controlled Trial
Actual Study Start Date : April 18, 2021
Estimated Primary Completion Date : March 31, 2024
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Active
A single dose of Tranexamic acid 500mg given by intramuscular injection
 Drug: Tranexamic Acid 500 MG
given once as an intramuscular injection
Placebo Comparator: Placebo
One Injection of the placebo which is 10 mL Sodium Chloride (0.9%)
 Drug: Tranexamic Acid 500 MG
given once as an intramuscular injection


Outcome Measures
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Primary Outcome Measures :
  1. Emergency department discharge [ Time Frame: within 24 hours ]
    discharge


Secondary Outcome Measures :
  1. Intracranial bleeding on CT scan [ Time Frame: within 48 hours ]
    any bleeding on the last scan conducted within 48 hours of randomisation

  2. Head injury related death [ Time Frame: within 48 hours ]
    In-hospital head injury-related death within 48 hours of injury

  3. All cause mortality [ Time Frame: within 28 days ]
    Cause of death will be described

  4. Disability [ Time Frame: within 28 days ]
    The Barthel scale will be used to assess functional disability

  5. Global assessment of ability to self-care [ Time Frame: within 28 days ]
    Scale of 1 to 5

  6. Neurosurgery [ Time Frame: within 28 days ]
    receipt of neurosurgery and type

  7. Days in ICU [ Time Frame: within 28 days ]
    Number of days

  8. Re-admission to hospital [ Time Frame: within 28 days ]
    readmission after discharge

  9. Vascular occlusive events [ Time Frame: within 28 days ]
    pulmonary embolism, myocardial infarction, deep vein thrombosis and stroke

  10. Seizures [ Time Frame: within 28 days ]
  11. Intramuscular injection site reaction [ Time Frame: within 28 days ]
    frequency and type of reactions

  12. Pneumonia [ Time Frame: within 28 days ]
  13. Adverse events [ Time Frame: within 28 days ]
    Any untoward medical occurrence (other than pre-specified outcomes)

  14. Dementia [ Time Frame: 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.


Eligibility Criteria
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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04521881


Contacts
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Contact: Haleema Shakur-Still +4407714139500 Haleema.Shakur@lshtm.ac.uk

Locations
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United Kingdom
The Royal London Hospital Recruiting
London, United Kingdom, E1 1FR
Contact: Ben Bloom         
St George's Hospital Recruiting
London, United Kingdom, SW17 0QT
Contact: Heather Jarman         
Sponsors and Collaborators
London School of Hygiene and Tropical Medicine
Investigators
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Study Chair: Haleema Shakur-Still London School of Hygiene and Tropical Medicine
Study Chair: Ian Roberts London School of Hygiene and Tropical Medicine
More Information
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Additional Information:

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Responsible Party: London School of Hygiene and Tropical Medicine
ClinicalTrials.gov Identifier: NCT04521881    
Other Study ID Numbers: 2020-KEP-456
2020-003391-40 ( EudraCT Number )
First Posted: August 21, 2020    Key Record Dates
Last Update Posted: January 5, 2023
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Access Criteria: Totally anonymised data (without random allocation, patient, country and site identifiers) will be freely available.Where random allocation codes, country/site identifiers are requested, appropriate pre-specified analysis plan will need to be submitted to the Trial Management Group for review and if necessary, appropriate Ethics Committee approval will be required.
URL: http://freebird.lshtm.ac.uk

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by London School of Hygiene and Tropical Medicine:
Traumatic brain injury, tranexamic acid, older adults
Additional relevant MeSH terms:
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Brain Injuries
Brain Injuries, Traumatic
Wounds and Injuries
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
 Trauma, Nervous System
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants