Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children

Tranexamic acid (TXA), a drug that stops bleeding, is the only drug treatment that improves
survival in adults with serious bleeding after injuries. However, TXA has not been used
routinely in children with traumatic bleeding because no studies have appropriately evaluated
TXA for injured children. Such a study has the potential for significant impact in improving
the lives of injured children and their families, if found to be successful. The long-term
objective is to evaluate the benefits and risks of TXA in severely injured children. This
will be achieved by ultimately conducting two large-scale, multicenter, randomized controlled
trials of TXA use in severely injured children. One trial will evaluate TXA in children with
severe injuries to the body ("torso injuries", i.e., to the abdomen and chest) and the second
trial will evaluate TXA in children with moderate-to-severe traumatic brain injuries (TBIs).
However, conducting a clinical trial in critically ill children is challenging due to lower
disease frequency and complex parent consent/child assent procedures. The investigators will
conduct a pilot study, designed similarly to the full-scale trials but with much smaller
patient enrollment, to assess the feasibility of, and fill crucial information gaps for the
two subsequent large-scale clinical trials. Injured children will be randomized to one of
three study arms: two different TXA doses or placebo. The specific aim of the proposed pilot
study is to demonstrate the ability to efficiently identify and enroll children with
hemorrhagic torso injuries or TBIs into a multicenter, randomized controlled pilot study
evaluating these two doses of TXA and placebo. The pilot study will enroll 40 children who
meet inclusion and exclusion criteria at 4 participating sites. To demonstrate the ability to
collect outcome measures, the investigators will collect the identical anticipated outcome
measures for the subsequent clinical trials: total blood products transfused over the initial
48 hours of care (torso injury trial), and intracranial hemorrhage progression in first 24
hours and neurocognitive function at 6 months after randomization (TBI trial). The
investigators will also collect safety outcomes, specifically venothromboembolic events
(i.e., blot clots in the blood vessels) and seizures within the initial 24 hours of study
drug. Additional objectives of this pilot study are to: evaluate the ability to efficiently
screen, identify, consent, randomize, and initiate the study intervention within 3 hours of
injury, assess protocol adherence and variability of care in enrolled patients, and identify
operational efficiencies with the potential to enhance the success of the subsequent trials.

Inclusion Criteria:

1. Less than 18 years old AND

2. Penetrating torso trauma, blunt torso trauma, or head trauma as defined below.

3. Penetrating Torso Trauma:

a. Penetrating trauma to the chest, abdomen, neck, pelvis or thigh with at least one
of the following:

- age-adjusted hypotension, or

- age-adjusted tachycardia despite adequate resuscitation fluids, or

- radiographic evidence of internal hemorrhage, or

- clinician suspicion of ongoing internal hemorrhage

4. Blunt Torso Trauma (at least one of the following):

1. Clinician suspicion of hemorrhagic blunt torso injury and at least one of the
following:

- age-adjusted hypotension, or

- persistent age-adjusted tachycardia despite adequate resuscitation fluids

2. Hemothorax on chest tube placement or imaging,

3. Clinical suspicion of hemorrhagic blunt torso injury and Intraperitoneal fluid on
abdominal ultrasonography (Focused Assessment with Sonography in Trauma),

4. Intra-abdominal injury on CT with either contrast extravasation or more than
trace intraperitoneal fluid,

5. Pelvic fracture with contrast extravasation or hematoma on abdominal/pelvic CT
scan with at least one of the following:

- Age-adjusted tachycardia, or

- Age-adjusted hypotension.

5. Head Trauma:

1. Initial Glasgow Coma Scale (GCS) score 3 to 13 with associated intracranial
hemorrhage on cranial CT scan (enroll after cranial CT scan)

Exclusion Criteria:

1. Unable to administer study drug within 3 hours of traumatic event

2. Known pregnancy

3. Known prisoners

4. Known wards of the state

5. Cardiac arrest prior to randomization

6. GCS score of 3 with bilateral unresponsive pupils

7. Isolated subarachnoid hemorrhage, epidural hematoma, or diffuse axonal injury

8. Known bleeding/clotting disorders

9. Known seizure disorders

10. Known history of severe renal impairment

11. Suspected non-accidental trauma (child abuse)

12. Unknown time of injury

13. Previous enrollment into the TIC-TOC trial

14. Prior TXA for current injury

15. Non-English and non-Spanish speaking

16. Known venous or arterial thrombosis