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Original Investigation
October 5, 2020

Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury: A Double-blind, Placebo-Controlled, Randomized Clinical Trial

Author Affiliations
  • 1Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 2Division of Trauma and General Surgery, Department of Surgery, Pittsburgh Trauma Research Center, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 3Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 4Department of Surgery, University of Texas Health San Antonio, San Antonio
  • 5Department of Surgery, University of Utah, Salt Lake City
  • 6Department of Surgery, University of Arizona, Tucson
JAMA Surg. Published online October 5, 2020. doi:10.1001/jamasurg.2020.4350
Key Points

Question  Does prehospital administration of tranexamic acid compared with placebo result in lower 30-day mortality in patients at risk for hemorrhage after trauma?

Findings  In this multicenter randomized clinical trial of 927 patients, patients who received tranexamic acid compared with placebo in the prehospital setting did not have a significantly lower rate of 30-day mortality (8.1% vs 9.9%). There were no differences in the incidence of pulmonary embolism, deep vein thrombosis, seizures, or adverse events, including thrombotic complications, across arms.

Meaning  Prehospital administration of tranexamic acid is safe but does not significantly reduce mortality in patients at risk for hemorrhage after injury.

Abstract

Importance  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 ≤90 mm Hg) or tachycardia (heart rate ≥110/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 Measures  The 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 ≤70 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 Relevance  In 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 patients at risk for hemorrhage in the prehospital setting is safe and associated with survival benefit in specific subgroups of patients.

Trial Registration  ClinicalTrials.gov Identifier: NCT02086500

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