Prehospital Tranexamic Acid Use for Traumatic Brain Injury
Condition: Traumatic Brain Injury
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Wounds and Injuries
Intervention: 1 gram Tranexamic Acid (TXA); 2 grams TXA; 0.9% Sodium Chloride injectable
Intervention description: TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.; TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.; Loading dose of 0.9% Sodium Chloride solution given prior to hospital arrival followed by a placebo of 0.9% Sodium Chloride solution infusion over 8 hours after hospital arrival. No active drug is added to the solution.
Intervention MeSH terms: Tranexamic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 967.0
Sex: All
Minimum age: 15 Years
Healthy volunteers: No
Keywords: tranexamic acid; traumatic brain injury; intracranial hemorrhage; prehospital; neurologic outcome; glasgow outcome scale extended; disability rating scale

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Blunt or penetrating traumatic mechanism consistent with traumatic brain injury

          2. Prehospital Glasgow Coma Score (GCS) score ≤ 12 at any time prior to randomization and
             administration of sedative and/or paralytic agents

          3. Prehospital systolic blood pressure (SBP) ≥ 90 mmHg prior to randomization

          4. Prehospital intravenous (IV) or intraosseous (IO) access

          5. Estimated Age ≥ 15 (or estimated weight > 50 kg if age is unknown)

          6. Emergency Medicine System (EMS) transport to a participating trauma center

        Exclusion Criteria:

          1. Prehospital GCS=3 with no reactive pupil

          2. Estimated time from injury to hospital arrival > 2 hours

          3. Unknown time of injury - no known reference times to support estimation

          4. Clinical suspicion by EMS of seizure activity or known history of seizures, acute
             myocardial infarction (MI) or stroke

          5. Cardio-pulmonary resuscitation (CPR) by EMS prior to randomization

          6. Burns > 20% total body surface area (TBSA)

          7. Suspected or known prisoners

          8. Suspected or known pregnancy

          9. Prehospital TXA given prior to randomization

         10. Subjects who have activated the "opt-out" process when required by the local
             regulatory board