{"id":17,"date":"2020-09-04T13:15:08","date_gmt":"2020-09-04T13:15:08","guid":{"rendered":"https:\/\/crash4.lshtm.ac.uk\/?page_id=17"},"modified":"2022-09-16T09:06:22","modified_gmt":"2022-09-16T09:06:22","slug":"publications","status":"publish","type":"page","link":"https:\/\/crash4.lshtm.ac.uk\/index.php\/publications\/","title":{"rendered":"Publications"},"content":{"rendered":"\t\t
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2022<\/h3>

Collaborators, The CRASH-4<\/p>

Intramuscular tranexamic acid for symptomatic mild traumatic brain injury in older adults: a pilot randomised, placebo-controlled trial (The CRASH-4 trial pilot phase).<\/a> Journal Article<\/span> Forthcoming<\/span><\/p>

In: <\/span>Forthcoming.<\/p>

Abstract<\/a><\/span> | Links<\/a><\/span> | BibTeX<\/a><\/span> | Tags: <\/span><\/p>

@article{nokey,
\r\ntitle = {Intramuscular tranexamic acid for symptomatic mild traumatic brain injury in older adults:  a pilot randomised, placebo-controlled trial (The CRASH-4 trial pilot phase).},
\r\nauthor = {The CRASH-4 Collaborators},
\r\nurl = {https:\/\/crash4.lshtm.ac.uk\/wp-content\/uploads\/2022\/09\/CRASH-4-Pilot-phase-paper.pdf},
\r\nyear  = {2022},
\r\ndate = {2022-09-01},
\r\nurldate = {2022-09-01},
\r\nabstract = {Background
\r\nMild traumatic brain injury (TBI) can cause death, disability and dementia in older adults. Timely tranexamic acid (TXA) treatment, by preventing or limiting intracranial bleeding, could reduce these risks. The CRASH-4 trial will assess the effects of early intramuscular TXA in older adults with mild TBI. To test the trial procedures and the acceptability of the intervention, we conducted a pilot phase. 
\r\n
\r\nMethods
\r\nWe recruited patients aged 50 years or older if they had a history or signs (laceration, bruise, swelling or pain in head or face) of a head injury; a GCS \u2265 13; any impairment of consciousness and were within 3 hours of the injury. We enrolled patients at the scene of the injury or in the ambulance. We also enrolled patients who presented directly to the emergency department. We randomly allocated patients to receive an intramuscular injection of 500 mg tranexamic acid or matching placebo. We gave one 5mL injection (100mg\/ml TXA or placebo) or two 2.5mL injections depending on muscle mass. The objectives of the pilot were (1) to test all trial procedures, including the willingness of paramedics and emergency physicians to recruit patients and the willingness of patients to be enrolled, (2) to determine the rate of recruitment (number of patients per site per month), (3) to assess the acceptability of the intramuscular injection and (4) to determine event rates and rates of follow up.
\r\n
\r\nResults
\r\nWe recruited 493 patients between April 2021 and July 2022. Their mean age was 73 years (SD=12 years) and 246 (50%) of patients were female. The mean time from injury to randomization was 2.4 hours (SD=0.7 hours). The average recruitment rate was 1.7 patients per site per month. A single 5mL injection was received by 62% of patients and 38% of patients received two 2.5mL injections. An injection site reaction was reported in 4 patients, all of whom had bruising at the injection site (0.8%). There were 27 serious adverse events reported but none were suspected to be related to the trial treatment. Of the 483 randomised participants with outcome data, 54% were discharged from the emergency department within 24 h of their injury (n=261). Of the 220 patients that were admitted to hospital, 41% were admitted due to their head injury, 45% were admitted for another injury or medical condition, 4% were admitted while awaiting transfer to the community and 10% were admitted for other reasons. The average duration of hospital admission was 0.4 days (IQR=0.2-2.2). The average duration of admission was 4.6 days (IQR=2.1-10.7) for patients with intracranial haemorrhage compared to 0.4 days (IQR=0.2-1.8) for patients who did not. 43 patients had intracranial bleeding (9%), 3 had neurosurgery (0.6%) and 7 patients died (1.5%). 
\r\n
\r\nDiscussion
\r\nThe intramuscular injection (TXA or placebo) was well tolerated by older adults with mild TBI. Based on the observed recruitment and outcome event rates, a large trial of the efficacy and safety of early intramuscular tranexamic acid for older adults with mild traumatic brain injury appears feasible. 
\r\n
\r\nTrial registration: The trial is registered at ClinicalTrials.gov: NCT04521881 and EudraCT number: 2020-003391-40. 
\r\nKeywords: Antifibrinolytic; clinical trial; tranexamic acid; traumatic brain injury; intracranial bleeding. 
\r\n},
\r\nkeywords = {},
\r\npubstate = {forthcoming},
\r\ntppubtype = {article}
\r\n}
\r\n<\/pre><\/div>
Close<\/a><\/p><\/div>
Background
\r\nMild traumatic brain injury (TBI) can cause death, disability and dementia in older adults. Timely tranexamic acid (TXA) treatment, by preventing or limiting intracranial bleeding, could reduce these risks. The CRASH-4 trial will assess the effects of early intramuscular TXA in older adults with mild TBI. To test the trial procedures and the acceptability of the intervention, we conducted a pilot phase. 
\r\n
\r\nMethods
\r\nWe recruited patients aged 50 years or older if they had a history or signs (laceration, bruise, swelling or pain in head or face) of a head injury; a GCS \u2265 13; any impairment of consciousness and were within 3 hours of the injury. We enrolled patients at the scene of the injury or in the ambulance. We also enrolled patients who presented directly to the emergency department. We randomly allocated patients to receive an intramuscular injection of 500 mg tranexamic acid or matching placebo. We gave one 5mL injection (100mg\/ml TXA or placebo) or two 2.5mL injections depending on muscle mass. The objectives of the pilot were (1) to test all trial procedures, including the willingness of paramedics and emergency physicians to recruit patients and the willingness of patients to be enrolled, (2) to determine the rate of recruitment (number of patients per site per month), (3) to assess the acceptability of the intramuscular injection and (4) to determine event rates and rates of follow up.
\r\n
\r\nResults
\r\nWe recruited 493 patients between April 2021 and July 2022. Their mean age was 73 years (SD=12 years) and 246 (50%) of patients were female. The mean time from injury to randomization was 2.4 hours (SD=0.7 hours). The average recruitment rate was 1.7 patients per site per month. A single 5mL injection was received by 62% of patients and 38% of patients received two 2.5mL injections. An injection site reaction was reported in 4 patients, all of whom had bruising at the injection site (0.8%). There were 27 serious adverse events reported but none were suspected to be related to the trial treatment. Of the 483 randomised participants with outcome data, 54% were discharged from the emergency department within 24 h of their injury (n=261). Of the 220 patients that were admitted to hospital, 41% were admitted due to their head injury, 45% were admitted for another injury or medical condition, 4% were admitted while awaiting transfer to the community and 10% were admitted for other reasons. The average duration of hospital admission was 0.4 days (IQR=0.2-2.2). The average duration of admission was 4.6 days (IQR=2.1-10.7) for patients with intracranial haemorrhage compared to 0.4 days (IQR=0.2-1.8) for patients who did not. 43 patients had intracranial bleeding (9%), 3 had neurosurgery (0.6%) and 7 patients died (1.5%). 
\r\n
\r\nDiscussion
\r\nThe intramuscular injection (TXA or placebo) was well tolerated by older adults with mild TBI. Based on the observed recruitment and outcome event rates, a large trial of the efficacy and safety of early intramuscular tranexamic acid for older adults with mild traumatic brain injury appears feasible. 
\r\n
\r\nTrial registration: The trial is registered at ClinicalTrials.gov: NCT04521881 and EudraCT number: 2020-003391-40. 
\r\nKeywords: Antifibrinolytic; clinical trial; tranexamic acid; traumatic brain injury; intracranial bleeding. 
\r\n<\/div>
Close<\/a><\/p><\/div>