Does tranexamic acid improve outcomes in traumatic brain injury?

Mahmood, Abda; Roberts, Ian; Shakur, Haleema; Harris, Tim; Belli, Antonio

doi:10.1136/bmj.i4814

Cited by 11 publications

(2 citation statements)

References 28 publications

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“…Details of our search were published previously. 61 We found two small randomised trials of TXA in TBI with a total of 510 patients. Meta-analysis of the two trials showed a statistically significant reduction (RR 0.63, 95% CI 0.40 to 0.99) in death with TXA.…”

Section: Findings In Contextmentioning

confidence: 99%

Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT

Roberts

Shakur-Still

Aeron-Thomas³

et al. 2021

Health Technol Assess

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Background Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients. Objective To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness. Design Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model. Setting 175 hospitals in 29 countries. Participants Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible. Intervention Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. Main outcome measures Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events. Results Among patients treated within 3 hours of injury (n = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction (p-value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury (p = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury (p = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained). Conclusion Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive. Future work Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed. Limitations Time to treatment may have been underestimated. Trial registration Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277. Funding The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme.

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Section: Findings In Contextmentioning

confidence: 99%

Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT

Roberts

Shakur-Still

Aeron-Thomas³

et al. 2021

Health Technol Assess

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“…Tranexamic acid could penetrate the blood-brain-barrier to enter the cerebrospinal fluid 8, 9 , inhibit the enzymatic breakdown of fibrin blood clots and reduce intracranial haemorrhage expansion. A recent systematic review identified two completed randomised trials of tranexamic acid in TBI 10 . When the two trials were combined in a meta-analysis (n=478), there appears to be a statistically significant reduction in intracranial haemorrhage growth (RR 0.75, 95% CI 0.58–0.98; P = 0.03) and mortality (RR 0.63, 95% CI 0.40–0.99; P = 0.05) with tranexamic acid.…”

Section: Introductionmentioning

confidence: 99%

A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan

Mahmood¹,

Roberts²,

Shakur-Still³

2019

Wellcome Open Res

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Background: The CRASH-3 trial is a randomised trial on the effect of tranexamic acid (TXA) versus placebo on death and disability in traumatic brain injury (TBI). The CRASH-3 intracranial bleeding mechanistic study (IBMS) is a randomised trial nested within the CRASH-3 trial to examine the effect of TXA versus placebo on intracranial bleeding and infarction. Methods: Patients eligible for the CRASH-3 trial, with a GCS of 12 or less or intracranial bleeding on a pre-randomisation CT scan are eligible for the IBMS. The occurrence of intracranial bleeding, infarction, haemorrhagic oedematous lesions, mass effect and haemorrhage evacuation is examined within 28 days of randomisation using routinely collected brain scans. The primary outcome is the volume of intra-parenchymal bleeding in patients randomised within three hours of injury (adjusted for prognostic covariates). Secondary outcomes include a composite “poor” outcome, progressive and new intracranial bleeding, intracranial bleeding after neurosurgery and cerebral infarcts seen up to 28 days post-randomisation. All outcomes will be compared between treatment groups. Statistical analyses: The primary outcome will be analysed using a covariate adjusted linear mixed model. The same analysis will be done separately for patients who undergo haemorrhage evacuation post-randomisation. We will express the effect of TXA on the composite outcome, new and progressive bleeding using relative risks and 95% CIs, and on cerebral infarcts using hazard ratios and 95% CIs. We will conduct sensitivity analyses assuming missing data are MCAR or MNAR. Conclusion: The IBMS will provide information on the mechanism of action of TXA in TBI. This pre-specified statistical analysis plan is a technical extension of the published protocol. Trial registration: The CRASH-3 trial was prospectively registered at the International Standard Randomised Controlled Trials registry (19 July 2011) and ClinicalTrials.gov (25 July 2011). The registries were updated with details for the IBMS on 20 December 2016.

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Benefits of the tranexamic acid in head trauma with no extracranial bleeding: a prospective follow-up of 180 patients

Chakroun-Walha

Samet

Jerbi

et al. 2018

Eur J Trauma Emerg Surg

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Does tranexamic acid improve outcomes in traumatic brain injury?

Cited by 11 publications

References 28 publications

Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT

Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT

A nested randomised trial of the effect of tranexamic acid on intracranial haemorrhage and infarction in traumatic brain injury (CRASH-3 trial intracranial bleeding mechanistic study): Statistical analysis plan

Benefits of the tranexamic acid in head trauma with no extracranial bleeding: a prospective follow-up of 180 patients

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