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.

Conditions

• Traumatic Brain Injury

Interventions

DRUG

1 gram Tranexamic Acid (TXA)

TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.

DRUG

2 grams TXA

TXA produces an antifibrinolytic effect by competitively inhibiting the activation of plasminogen to plasmin.

DRUG

0.9% Sodium Chloride injectable

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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• U.S. Army Medical Research and Development Command

  collaborator FED

• Canadian Institutes of Health Research (CIHR)

  collaborator OTHER_GOV

• Heart and Stroke Foundation of Canada

  collaborator OTHER

• American Heart Association

  collaborator OTHER

• Defence Research and Development Canada

  collaborator INDUSTRY

• University of Washington

  lead OTHER

Principal Investigators

• Susanne May, PhD · University of Washington

• Martin Schreiber, MD FACS · Oregon Health and Science University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

15 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2015-05-31

Primary Completion

2017-11-07

Completion

2017-11-07

Countries

• United States
• Canada

Study Locations