Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury

Abstract

In-hospital administration of tranexamic acid after injury improves outcomes in patients at risk for hemorrhage. Data demonstrating the benefit and safety of the pragmatic use of tranexamic acid in the prehospital phase of care are lacking for these patients.OBJECTIVE To assess the effectiveness and safety of tranexamic acid administered before hospitalization compared with placebo in injured patients at risk for hemorrhage.DESIGN, SETTING, AND PARTICIPANTS This pragmatic, phase 3, multicenter, double-blind, placebo-controlled, superiority randomized clinical trial included injured patients with prehospital hypotension (systolic blood pressure Յ90 mm Hg) or tachycardia (heart rate Ն110/min) before arrival at 1 of 4 US level 1 trauma centers, within an estimated 2 hours of injury, from May 1, 2015, through October 31, 2019.INTERVENTIONS Patients received 1 g of tranexamic acid before hospitalization (447 patients) or placebo (456 patients) infused for 10 minutes in 100 mL of saline. The randomization scheme used prehospital and in-hospital phase assignments, and patients administered tranexamic acid were allocated to abbreviated, standard, and repeat bolus dosing regimens on trauma center arrival. MAIN OUTCOMES AND MEASURESThe primary outcome was 30-day all-cause mortality.RESULTS In all, 927 patients (mean [SD] age, 42 [18] years; 686 [74.0%] male) were eligible for prehospital enrollment (460 randomized to tranexamic acid intervention; 467 to placebo intervention). After exclusions, the intention-to-treat study cohort comprised 903 patients: 447 in the tranexamic acid arm and 456 in the placebo arm. Mortality at 30 days was 8.1% in patients receiving tranexamic acid compared with 9.9% in patients receiving placebo (difference, -1.8%; 95% CI, -5.6% to 1.9%; P = .17). Results of Cox proportional hazards regression analysis, accounting for site, verified that randomization to tranexamic acid was not associated with a significant reduction in 30-day mortality (hazard ratio, 0.81; 95% CI, 0.59-1.11, P = .18). Prespecified dosing regimens and post-hoc subgroup analyses found that prehospital tranexamic acid were associated with significantly lower 30-day mortality. When comparing tranexamic acid effect stratified by time to treatment and qualifying shock severity in a post hoc comparison, 30-day mortality was lower when tranexamic acid was administered within 1 hour of injury (4.6% vs 7.6%; difference, −3.0%; 95% CI, −5.7% to −0.3%; P < .002). Patients with severe shock (systolic blood pressure Յ70 mm Hg) who received tranexamic acid demonstrated lower 30-day mortality compared with placebo (18.5% vs 35.5%; difference, −17%; 95% CI, −25.8% to −8.1%; P < .003). CONCLUSIONS AND RELEVANCEIn injured patients at risk for hemorrhage, tranexamic acid administered before hospitalization did not result in significantly lower 30-day mortality. The prehospital administration of tranexamic acid after injury did not result in a higher incidence of thrombotic complications or adverse events. Tranexamic acid given to injured patient...

Validation of the BATT score for prehospital risk stratification of traumatic haemorrhagic&nbsp;death: Usefulness for tranexamic acid treatment&nbsp;criteria.

“…Furthermore, we are reassured by the result of the STAAMP trial assessing TXA in trauma patient in the prehospital setting. [25] The magnitude of the treatment effect observed in this trial is similar to that observed in the CRASH-2 trial although the estimate was more imprecise.…”

“…[4,17,[31][32][33] Recent trials in prehospital trauma did not nd any increase in vascular occlusive events associated with TXA and provide evidence for applicability of TXA treatment in the prehospital setting. [25,34] Recent research has found that TXA is well tolerated and rapidly absorbed after intramuscular injection reaching therapeutic concentrations within 15 minutes in bleeding trauma patients. [35] Further research is needed to assess the cost-effectiveness of different treatment thresholds and whether use of the BATT score and intramuscular TXA administration by paramedics increases the pre-hospital administration of TXA to patients at risk of bleeding from trauma.…”

Efficacy and Safety of Tranexamic Acid in Emergency Trauma: A Systematic Review and Meta-Analysis

“…From those studies, we only included thirty-seven trials for full-text evaluation. Finally, 17 studies were found to be eligible for quantitative analysis [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 ]. The details of the selected trials are summarized in Table 1 and Table S1 .…”

The European Perspective on the Management of Acute Major Hemorrhage and Coagulopathy after Trauma: Summary of the 2019 Updated European Guideline

“…According to the dose regimen in the CRASH-2 trial [ 39 ], tranexamic acid is given early to bleeding trauma patients or at risk for significant hemorrhage as 1 g bolus intravenously within 3 h of injury followed by another 1 g as infusion over 8 h (R22/1A). To date, TXA is considered a principal component to a range of massive transfusion protocols and algorithms, although the two most recent randomized trials using TXA prehospital in the setting of trauma [ 40 ] and traumatic brain injury [ 41 ] have failed to reproduce the beneficial effects of TXA seen in earlier studies for 30-day mortality and neurologic outcome at six months. However, when comparing the TXA effect stratified by time to treatment and qualifying shock severity in a post hoc comparison, 30-day mortality was lower when TXA was administered within 1 h of injury (4.6% vs. 7.6%; difference, −3.0%; 95%CI, −5.7% to −0.3%; p < 0.002) and in patients with severe shock (18.5% vs. 35.5%; difference, −17%; 95%CI, −25.8% to −8.1%; p < 0.003; [ 40 ]).…”

“…To date, TXA is considered a principal component to a range of massive transfusion protocols and algorithms, although the two most recent randomized trials using TXA prehospital in the setting of trauma [ 40 ] and traumatic brain injury [ 41 ] have failed to reproduce the beneficial effects of TXA seen in earlier studies for 30-day mortality and neurologic outcome at six months. However, when comparing the TXA effect stratified by time to treatment and qualifying shock severity in a post hoc comparison, 30-day mortality was lower when TXA was administered within 1 h of injury (4.6% vs. 7.6%; difference, −3.0%; 95%CI, −5.7% to −0.3%; p < 0.002) and in patients with severe shock (18.5% vs. 35.5%; difference, −17%; 95%CI, −25.8% to −8.1%; p < 0.003; [ 40 ]). While there was no increased risk of thromboembolic events observed with the conventional CRASH-2 dose regimen, these were more seen in the group that was treated with 2 g TXA bolus (9% versus 4%; [ 41 ]).…”