Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children: An Efficacy Study

NCT04387305 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 128206
• Study Type: interventional
• Target: 2,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

Trauma is the leading cause of death and disability in children in the United States. The objective of this study is to evaluate the benefits and harms of tranexamic acid (TXA; a drug that stops bleeding) in severely injured children with hemorrhagic brain and/or torso injuries. Using thromboelastography, we will measure baseline fibrinolysis to assess for treatment effects of TXA at different levels of fibrinolysis.

Conditions

Brain Injuries, Traumatic; Wounds and Injury; Hemorrhage; Trauma Injury

Keywords

Tranexamic acid; Brain Injuries; Hemorrhage; Clinical Trial; Children; Pediatric; Trauma

Outcome Measures

Primary Outcomes (1)

• Pediatric Quality of Life Inventory (PedsQL) area under the curve

  Neurocognitive functioning and quality-of-life measure; 0 to 100 with higher scores representing better outcomes

  1 week, 1 month, 3 months, and 6 months (as measured as an area under the curve)

Secondary Outcomes (3)

• Intracranial hemorrhage progression

  24 hours (±6 hours)

• Blood transfusion

  First 48 hours after randomization

• PedsQL Physical Domain area under the curve

  1 week, 1 month, 3 months, and 6 months

Other Outcomes (8)

• Glasgow Outcome Scale-Extended (GOS-E) Peds

  1 week, 1 month, 3 months, and 6 months

• Pediatric Quality of Life Inventory (PedsQL) Multidimensional Fatigue Scale

  1 week, 1 month, 3 months, and 6 months

• D-dimer

  Change from baseline to end of 8-hour study drug infusion

Study Arms (4)

Tranexamic acid 15 mg/kg bolus

EXPERIMENTAL

Subjects will receive a 15 mg/kg bolus of tranexamic acid over 30 minutes followed by a 2 mg/kg/h infusion over 8 hours. This represents 31 mg/kg total dose of TXA.

Drug: Tranexamic acid injection

Tranexamic acid 30 mg/kg bolus

EXPERIMENTAL

Subjects will receive a 30 mg/kg bolus of tranexamic acid over 30 minutes followed by a 4 mg/kg/h infusion over 8 hours. This represents 62 mg/kg total dose of TXA.

Drug: Tranexamic acid injection

Tranexamic acid 45 mg/kg bolus

EXPERIMENTAL

Subjects will receive a 45 mg/kg bolus of tranexamic acid over 30 minutes followed by a 6 mg/kg/h infusion over 8 hours. This represents 91 mg/kg total dose of TXA. This dosing arm will only open if a dose-effect is determined based on accumulating data.

Drug: Tranexamic acid injection

Placebo

PLACEBO COMPARATOR

Subjects in the placebo group will receive a bolus dose of normal saline over 10 minutes followed by a normal saline infusion over 8 hours

Drug: Tranexamic acid injection

Interventions

Tranexamic acid injection DRUG

Active drug is provided to participants as described based on the TXA arm they are randomized to.

Placebo; Tranexamic acid 15 mg/kg bolus; Tranexamic acid 30 mg/kg bolus; Tranexamic acid 45 mg/kg bolus

Eligibility Criteria

• Age: 0 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Less than 18 years old AND
• Penetrating torso trauma, blunt torso trauma, or head trauma as defined below:
• Penetrating Torso Trauma:
• a. Penetrating trauma to the chest, abdomen, neck, or pelvis 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
• Blunt Torso Trauma:
• Clinician suspicion of hemorrhagic blunt torso injury and at least one of the following:
• age-adjusted hypotension, or
• age-adjusted tachycardia despite adequate resuscitation fluids
• Hemothorax on chest tube placement or imaging,
• Clinical suspicion of hemorrhagic blunt torso injury and Intraperitoneal fluid on abdominal ultrasonography (Focused Assessment with Sonography in Trauma),
• Intra-abdominal injury on CT with either contrast extravasation or more than trace intraperitoneal fluid,

You may not qualify if:

• Unable to administer study drug within 3 hours of traumatic event
• Known pregnancy
• Known ward of the state
• Cardiac arrest prior to randomization
• GCS score of 3 with bilateral unresponsive pupils
• Isolated subarachnoid hemorrhage, epidural hematoma, or diffuse axonal injury
• Known venous or arterial thrombosis
• Known bleeding/clotting disorders
• Known seizure disorders
• Known history of severe renal impairment
• Known allergy to TXA
• Unknown time of injury (includes suspected non-accidental trauma)
• Previous enrollment into the TIC-TOC trial
• Prior TXA for current injury
• Prior opt-out

Sponsors & Collaborators

• Daniel Nishijima, MD, MAS: lead
• Pediatric Emergency Care Applied Research Network: collaborator

Related Publications (3)

• Nishijima DK, Gosdin M, Naz H, Tancredi DJ, Hewes HA, Myers SR, Stanley RM, Adelson PD, Burd RS, Finkelstein Y, VanBuren J, Casper TC, Kuppermann N; TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN). Assessment of primary outcome measures for a clinical trial of pediatric hemorrhagic injuries. Am J Emerg Med. 2021 May;43:210-216. doi: 10.1016/j.ajem.2020.03.001. Epub 2020 Mar 9.

  PMID: 32278572 RESULT

• Trappey AF 3rd, Thompson KM, Kuppermann N, Stephenson JT, Nuno MA, Hewes HA, Meyers SR, Stanley RM, Galante JM, Nishijima DK; Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) Collaborators of the Pediatric Emergency Care Applied Research Network (PECARN). Development of transfusion guidelines for injured children using a Modified Delphi Consensus Process. J Trauma Acute Care Surg. 2019 Oct;87(4):935-943. doi: 10.1097/TA.0000000000002432.

  PMID: 31299040 RESULT

• Powers PE, Shore KK, Perez S, Ritley D, Kuppermann N, Holmes JF, Tzimenatos LS, Shawargga H, Nishijima DK. Public Deliberation as a Novel Method for an Exception From Informed Consent Community Consultation. Acad Emerg Med. 2019 Oct;26(10):1158-1168. doi: 10.1111/acem.13827. Epub 2019 Jul 24.

  PMID: 31271691 RESULT

Related Links

• TIC-TOC trial website

MeSH Terms

Conditions

Brain Injuries, Traumatic; Wounds and Injuries; Hemorrhage; Accidental Injuries; Brain Injuries

Interventions

Tranexamic Acid

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanecarboxylic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Daniel K Nishijima, MD, MAS

  University of California, Davis

  PRINCIPAL INVESTIGATOR

• Nathan Kuppermann, MD, MPH

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel K Nishijima, MD, MAS

CONTACT

916.734.3884; dnishijima@ucdavis.edu

Nathan Kuppermann, MD, MPH

CONTACT

916.734.1535; nkuppermann@ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: Bayesian adaptive response

Study Record Dates

• First Submitted: May 5, 2020
• First Posted: May 13, 2020
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): March 31, 2031
• Study Completion (Estimated): March 31, 2031
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 12 months after publication of primary manuscript.
• Access Criteria: Approval through NIH and PECARN