Prehospital Tranexamic Acid Use for Traumatic Brain Injury

• Status: Completed
• Trial end date: 2017-11-07
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Washington
• Collaborators: American Heart Association; Canadian Institutes of Health Research (CIHR); Defence Research and Development Canada; Heart and Stroke Foundation of Canada; National Heart, Lung, and Blood Institute (NHLBI); U.S. Army Medical Research and Development Command; U.S. Army Medical Research and Materiel Command
• Treatments: Pharmaceutical Solutions; Tranexamic Acid

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