Prehospital Tranexamic Acid Use for Traumatic Brain Injury

Summary

Primary aim: To determine the efficacy of two dosing regimens of TXA initiated in the prehospital setting in patients with moderate to severe TBI (GCS score ≤12). Primary hypothesis: The null hypothesis is that random assignment to prehospital administration of TXA in patients with moderate to severe TBI will not change the proportion of patients with a favorable long-term neurologic outcome compared to random assignment to placebo, based on the GOS-E at 6 months. Secondary aims: To determine differences between TXA and placebo in the following outcomes for patients with moderate to severe TBI treated in the prehospital setting with 2 dosing regimens of TXA: * Clinical outcomes: ICH progression, Marshall and Rotterdam CT classification scores, DRS at discharge and 6 months, GOS-E at discharge, 28-day survival, frequency of neurosurgical interventions, and ventilator-free, ICU-free, and hospital-free days. * Safety outcomes: Development of seizures, cerebral ischemic events, myocardial infarction, deep venous thrombosis, and pulmonary thromboembolism. * Mechanistic outcomes: Alterations in fibrinolysis based on fibrinolytic pathway mediators and degree of clot lysis based on TEG. Inclusion: Blunt and penetrating traumatic mechanism consistent with TBI with prehospital GCS ≤ 12 prior to administration of sedative and/or paralytic agents, prehospital SBP ≥ 90 mmHg, prehospital intravenous (IV) access, age ≥ 15yrs (or weight ≥ 50kg if age is unknown), EMS transport destination based on standard local practices determined to be a participating trauma center. Exclusion: Prehospital GCS=3 with no reactive pupil, estimated time from injury to start of study drug bolus dose \>2 hours, unknown time of injury, clinical suspicion by EMS of seizure activity, acute MI or stroke or known history, to the extent possible, of seizures, thromboembolic disorders or renal dialysis, CPR by EMS prior to randomization, burns \> 20% TBSA, suspected or known prisoners, suspected or known pregnancy, prehospital TXA or other pro-coagulant drug given prior to randomization, subjects who have activated the "opt-out" process when required by the local regulatory board. A multi-center double-blind randomized controlled trial with 3 treatment arms: * Bolus/maintenance: 1 gram IV TXA bolus in the prehospital setting followed by a 1 gram IV maintenance infusion initiated on hospital arrival and infused over 8 hours. * Bolus only: 2 grams IV TXA bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours. * Placebo: Placebo IV bolus in the prehospital setting followed by a placebo maintenance infusion initiated on hospital arrival and infused over 8 hours.

Timeline

Start

2015-05

Primary completion

2017-11-07

Completion

2017-11-07

Publications

• Minoza KG, Brito AM, Loss L, McLoud S, Kenny JEH, McLean WJ, Papa L, Rowell S, Schreiber M. Association between coagulation biomarkers, intracranial hemorrhage types, and tranexamic acid treatments in early traumatic brain injury. J Trauma Acute Care Surg. 2025 Sep 1;99(3):468-476. doi: 10.1097/TA.0000000000004669. Epub 2025 Jun 10.
• Newman ZC, Ogbeifun VO, Barbosa CE, McKinley WI, Benjamin AJ, Munar MY, Pramuka PE, McGovern KD, Nordgren RK, Schreiber MA, Rowell SE. Intravenous Versus Intraosseous Use of Tranexamic Acid in Patients With Traumatic Brain Injury. J Surg Res. 2024 Oct;302:798-804. doi: 10.1016/j.jss.2024.08.003. Epub 2024 Sep 2.
• Rowell S, Meier EN, Hoyos Gomez T, Fleming M, Jui J, Morrison L, Bulger E, Sopko G, Weisfeldt M, Christenson J, Klotz P, McMullan J, Callum J, Sheehan K, Tibbs B, Aufderheide T, Cotton B, Gandhi R, Idris A, Frascone RJ, Ferrara M, Richmond N, Kannas D, Schlamp R, Robinson B, Dries D, Tallon J, Hendrickson A, Gamber M, Garrett J, Simonson R, McKinley WI, Schreiber M. The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: A subgroup analysis from the prehospital TXA for TBI trial. J Trauma Acute Care Surg. 2024 Oct 1;97(4):572-580. doi: 10.1097/TA.0000000000004354. Epub 2024 Apr 30.
• Hoefer LE, Benjamin AJ, Polcari AM, Schreiber MA, Zakrison TL, Rowell SE. TXA does not affect levels of TBI-related biomarkers in blunt TBI with ICH: A secondary analysis of the prehospital TXA for TBI trial. J Trauma Acute Care Surg. 2024 Jan 1;96(1):94-100. doi: 10.1097/TA.0000000000004130. Epub 2023 Oct 9.
• Harmer JW, Dewey EN, Meier EN, Rowell SE, Schreiber MA. Tranexamic acid is not inferior to placebo with respect to adverse events in suspected traumatic brain injury patients not in shock with a normal head computed tomography scan: A retrospective study of a randomized trial. J Trauma Acute Care Surg. 2022 Jul 1;93(1):98-105. doi: 10.1097/TA.0000000000003635. Epub 2022 Mar 28.
• Rowell SE, Meier EN, McKnight B, Kannas D, May S, Sheehan K, Bulger EM, Idris AH, Christenson J, Morrison LJ, Frascone RJ, Bosarge PL, Colella MR, Johannigman J, Cotton BA, Callum J, McMullan J, Dries DJ, Tibbs B, Richmond NJ, Weisfeldt ML, Tallon JM, Garrett JS, Zielinski MD, Aufderheide TP, Gandhi RR, Schlamp R, Robinson BRH, Jui J, Klein L, Rizoli S, Gamber M, Fleming M, Hwang J, Vincent LE, Williams C, Hendrickson A, Simonson R, Klotz P, Sopko G, Witham W, Ferrara M, Schreiber MA. Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury. JAMA. 2020 Sep 8;324(10):961-974. doi: 10.1001/jama.2020.8958.

Drugs

Indications