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Background: The CRASH-3 trial hypothesised that timely tranexamic acid (TXA) treatment might reduce deaths from intracranial bleeding after traumatic brain injury (TBI). To explore the mechanism of action of TXA in TBI, we examined the timing of its effect on death.Methods: The CRASH-3 trial randomised 9202 patients within 3 h of injury with a GCS score ≤ 12 or intracranial bleeding on CT scan and no significant extracranial bleeding to receive TXA or placebo. We conducted an exploratory analysis of the effects of TXA on all-cause mortality within 24 h of injury and within 28 days, excluding patients with a GCS score of 3 or bilateral unreactive pupils, stratified by severity and country income. We pool data from the CRASH-2 and CRASH-3 trials in a one-step fixed effects individual patient data meta-analysis.Results: There were 7637 patients for analysis after excluding patients with a GCS score of 3 or bilateral unreactive pupils. Of 1112 deaths, 23.3% were within 24 h of injury (early deaths). The risk of early death was reduced with TXA (112 (2.9%) TXA group vs 147 (3.9%) placebo group; risk ratio [RR] RR 0.74, 95% CI 0.58-0.94). There was no evidence of heterogeneity by severity (p = 0.64) or country income (p = 0.68). The risk of death beyond 24 h of injury was similar in the TXA and placebo groups (432 (11.5%) TXA group vs 421 (11.7%) placebo group; RR 0.98, 95% CI 0.69-1.12). The risk of death at 28 days was 14.0% in the TXA group versus 15.1% in the placebo group (544 vs 568 events; RR 0.93, 95% CI 0.83-1.03). When the CRASH-2 and CRASH-3 trial data were pooled, TXA reduced early death (RR 0.78, 95% CI 0.70-0.87) and death within 28 days (RR 0.88, 95% CI 0.82-0.94).Conclusions: Tranexamic acid reduces early deaths in non-moribund TBI patients regardless of TBI severity or country income. The effect of tranexamic acid in patients with isolated TBI is similar to that in polytrauma. Treatment is safe and even severely injured patients appear to benefit when treated soon after injury.Trial Registration: ISRCTN15088122 , registered on 19 July 2011; NCT01402882 , registered on 26 July 2011. [ABSTRACT FROM AUTHOR]

Background: Each year world-wide about 65 million people sustain a mild traumatic brain injury (mTBI). Fatigue is a common and distressing symptom after mTBI. We examine the effect of tranexamic acid (TXA) on fatigue in patients with mTBI using data from the CRASH-3 trial., Methods: The CRASH-3 trial randomised 9,202 patients with traumatic brain injury and no significant extracranial bleeding to receive TXA or placebo within 3 hours of injury. The primary outcome was death from head injury within 28 days of injury. The methods and results are presented elsewhere. Fatigue was recorded as "None", "Moderate" or "Extreme." This study examines the effect of TXA on extreme fatigue in the 2,632 patients with mTBI (Glasgow Coma Scale [GCS] score≥13). Our analyses were not prespecified., Results: Our study primary outcome, extreme fatigue, was reported for 10 (0.8%) of 1,328 patients receiving TXA and 19 (1.5%) of 1,288 patients receiving placebo (risk ratio [RR]=0.51, 95% confidence interval [CI] 0.24-1.09). Death within 28 days of injury was reported for 34 (2.6%) of 1,328 patients receiving TXA versus 47 (3.6%) of 1,288 patients receiving placebo (RR=0.70, 95% CI 0.45-1.08). Among patients allocated to TXA, 44 (3.3%) patients either died or reported extreme fatigue versus 66 (5.1%) patients among those allocated to placebo (RR=0.65, 95% CI 0.44-0.94). This composite outcome is disproportionately influenced by deaths which account for 74% (81 from 110) of events., Conclusions: We found no evidence that tranexamic acid reduces fatigue in patients with mTBI. Given, 1) our analyses were not prespecified, 2) our outcome measure is not based on a validated fatigue severity scale, and 3) TBI patients can suffer from hospital-induced delirium, which hinders clinician assessment, these results need to be replicated in another study., Registration: ISRCTN (ISRCTN15088122, 19/07/2011), ClinicalTrials.gov (NCT01402882, 26/07/2011), EudraCT (2011-003669-14, 25/07/2011), Pan African Clinical Trial Registry (PACTR20121000441277, 30/10/2012)., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Mansukhani R et al.)

Background: Tranexamic acid (TXA) reduces the risk of death and is recommended as a treatment for women with severe postpartum bleeding. There is hope that giving TXA shortly before or immediately after birth could prevent postpartum bleeding. Extending the use of TXA to prevent harmful postpartum bleeding could improve outcomes for millions of women; however we must carefully consider the balance of benefits and potential harms. This article describes the protocol for a systematic review and individual patient data (IPD) meta-analysis to assess the effectiveness and safety of TXA for preventing postpartum bleeding in all women giving birth, and to explore how the effects vary by underlying risk and other patient characteristics.   Methods: We will search for prospectively registered, randomised controlled trials involving 500 patients or more assessing the effects of TXA in women giving birth. Two authors will extract data and assess risk of bias. IPD data will be sought from eligible trials. Primary outcomes will be life-threatening bleeding and thromboembolic events. We will use a one-stage model to analyse the data. Subgroup analyses will be conducted to explore whether the effectiveness and safety of TXA varies by underlying risk, type birth, maternal haemoglobin (Hb), and timing of TXA. This protocol is registered on PROSPERO (CRD42022345775).  Conclusions: This systematic review and IPD meta-analysis will address important clinical questions about the effectiveness and safety of the use of TXA for the prevention of postpartum bleeding that cannot be answered reliably using aggregate data and will inform the decision of who to treat.   PROSPERO registration: CRD42022345775  Keywords   Anti-fibrinolytics; Tranexamic acid; childbirth; postpartum haemorrhage; meta-analysis., Competing Interests: Competing interests: LS reports receiving lecture and consulting fees from Ferring. No competing interests were disclosed for any other author., (Copyright: © 2023 The Anti-fibrinolytics Trialists Collaborators – Obstetric Trialists Group et al.)

Background: Worldwide, traumatic brain injury (TBI) kills or hospitalises over 10 million people each year. Early intracranial bleeding is common after TBI, increasing the risk of death and disability. Tranexamic acid reduces blood loss in surgery and death due to bleeding in trauma patients with extra-cranial injury. Early administration of tranexamic acid in TBI patients might limit intracranial bleeding, reducing death and disability. The CRASH-3 trial aims to provide evidence on the effect of tranexamic acid on death and disability in TBI patients. We will randomly allocate about 13,000 TBI patients (approximately 10,000 within 3 hours of injury) to an intravenous infusion of tranexamic acid or matching placebo in addition to usual care. This paper presents a protocol update (version 2.1) and statistical analysis plan for the CRASH-3 trial. Results: The primary outcome is head injury death in hospital within 28 days of injury for patients treated within 3 hours of injury (deaths in patients treated after 3 hours will also be reported). Because there are reasons to expect that tranexamic acid will be most effective in patients treated immediately after injury and less effective with increasing delay, the effect in patients treated within one hour of injury is of particular interest. Secondary outcomes are all-cause and cause-specific mortality, vascular occlusive events, disability based on the Disability Rating Scale and measures suggested by patient representatives, seizures, neurosurgical intervention, neurosurgical blood loss, days in intensive care and adverse events. Sub-group analyses will examine the effect of tranexamic acid on head injury death stratified by time to treatment, severity of TBI and baseline risk. Conclusion: The CRASH-3 trial will provide reliable evidence of the effectiveness and safety of tranexamic acid in patients with acute TBI. Registration: International Standard Randomised Controlled Trials registry ( ISRCTN15088122) 19/07/2011, and ClinicalTrials.gov ( NCT01402882) 25/07/2011., Competing Interests: No competing interests were disclosed.