Brain Injuries, TraumaticPhase 3TIC-TOCNCT04387305
Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children: An Efficacy Study
A Phase 3 study testing Tranexamic acid injection in people with Brain Injuries, Traumatic and Wounds and Injury, run by Daniel Nishijima, MD, MAS.
Trial 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. Read more about this study
- Who is it for?
- Ages 0 to 17 years
- Conditions the study is for
- Brain Injuries, Traumatic, Wounds and Injury, Hemorrhage
- What is being tested?
- Tranexamic acid injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2,000 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2026to 31 Mar 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Less than 18 years old AND
- Penetrating torso trauma, blunt torso trauma, or head trauma as defined below:
- Penetrating Torso Trauma:
- 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
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- 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,
- Pelvic fracture with contrast extravasation or hematoma on abdominal/pelvic CT scan with at least one of the following:
- Age-adjusted hypotension, or
- Age-adjusted tachycardia.
- Head Trauma:
- Initial Glasgow Coma Scale (GCS) score 3 to 13 with associated intracranial hemorrhage on cranial CT scan (enroll after cranial CT scan)
Who cannot join
- 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
Show all 16Show fewer
- 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
- Non-English and non-Spanish speaking
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC): An Efficacy Study
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.
Read the detailed description
The TIC-TOC efficacy trial is a multicenter, adaptive allocation, randomized controlled trial of children younger than 18 years with hemorrhagic injuries to the torso and/or brain to evaluate the efficacy of TXA on functional outcome as measured by the PedsQL. Children will be randomized to one of three arms: 1) TXA 15 mg/kg bolus over 30 minutes, followed by a 2 mg/kg/hr infusion over 8 hours), 2) TXA 30 mg/kg bolus over 30 minutes, followed by a 4 mg/kg/hr infusion over 8 hours), and 3) normal saline placebo. A third TXA dose (45 mg/kg bolus dose over 30 minutes, followed by a 6 mg/kg/hr infusion over 8 hours) may be added later in the trial if a dose effect based on accumulating data is noted. The trial will be conducted in the Pediatric Emergency Care Applied Research Network (PECARN) across 40 sites over 4 years of enrollment for a maximum sample size of 2000 patients.
A Bayesian adaptive randomization design will be used to evaluate the efficacy of TXA in children with hemorrhagic brain and/or torso injuries. Because different types of injury have different pathophysiology and potential response to TXA, three different injury strata will be evaluated: isolated hemorrhagic brain injury, isolated hemorrhagic torso injury, and both hemorrhagic brain and torso injuries. The efficacy of TXA will be analyzed across all enrolled children as well as across each type of injury.
The Bayesian adaptive trial design also efficiently evaluates the effectiveness of TXA across different TXA doses. The trial will randomize the first 500 patients to two doses of TXA and placebo at a fixed 1:1:1 ratio. Interim analyses will be conducted when 500, 750, 1000, 1250, 1500, and 1750 patients have been enrolled. At each interim analysis, randomization probabilities will be adjusted in order to preferentially allocate patients to better performing doses, while allocation to the placebo arm will stay fixed. The adaptive randomization will be based entirely on pre-planned rules using accumulating data. A Bayesian hierarchical model will be used to estimate the treatment effect for each of the injury types to be informed by the data accumulated from all injury types. At interim analyses, if a dose effect is noted towards the higher dose of TXA (30 mg/kg bolus then a 4 mg/kg/hr infusion) being more efficacious using pre-specified criteria, then a higher dose study arm (TXA 45 mg/kg bolus then a 6 mg/kg/hr infusion) will be opened later in the trial. If the dose response curve is flat, suggesting that TXA is ineffective, then futility stopping rules can end the trial early.
- Being tested
- Tranexamic acid injection
- Keywords
- Tranexamic acid, Brain Injuries, Hemorrhage, Clinical Trial, Children, Pediatric, Trauma
- Medical subject headings
- Brain Injuries, Traumatic, Wounds and Injuries, Hemorrhage, Accidental Injuries, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tranexamic acid injectionDrug
Active drug is provided to participants as described based on the TXA arm they are randomized to.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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 Receives: Drug: Tranexamic acid injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 1 week, 1 month, 3 months, and 6 months (as measured as an area under the curve)
Secondary outcomes (3)
Intracranial hemorrhage progression
Intracranial hemorrhage progression on cranial computed tomography imaging
Measured: 24 hours (±6 hours)
Blood transfusion
Total volume of packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate
Measured: First 48 hours after randomization
PedsQL Physical Domain area under the curve
Physical domain of the PedsQL measure; 0 to 100 with higher scores representing better outcomes
Measured: 1 week, 1 month, 3 months, and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2020
- Study start1 Oct 2026 (estimated)
- Primary completion31 Mar 2031 (estimated)
- Study completion31 Mar 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Brain Injuries, TraumaticStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Bayesian adaptive response
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 2,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Daniel Nishijima, MD, MAS
- Sponsor type
- University, hospital or other
- Collaborators
- Pediatric Emergency Care Applied Research Network
- Responsible party
- Sponsor-investigator, Daniel Nishijima, MD, MAS, University of California, Davis
- Investigators
- Daniel K Nishijima, MD, MAS, Principal investigator, University of California, DavisNathan Kuppermann, MD, MPH, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04387305
- Sponsor's protocol ID
- 128206
- Acronym
- TIC-TOC
- Status last verified
- Dec 2025
- First submitted
- 5 May 2020
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: A public use database will be produced and will be completely de-identified in accordance with the definitions provided in the Health Insurance Portability and Accountability Act (HIPAA).
Publications
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.
PubMed 32278572Trappey 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.
PubMed 31299040Powers 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.
PubMed 31271691
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC): An Efficacy Study
- ClinicalTrials.gov ID
- NCT04387305
- Acronym / sponsor ID
- TIC-TOC / 128206
- Keywords
- Tranexamic acid, Brain Injuries, Hemorrhage, Clinical Trial, Children, Pediatric, Trauma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 2,000 participants (estimated)
- Lead sponsor
- Daniel Nishijima, MD, MASUniversity, hospital or other
- Collaborators
- Pediatric Emergency Care Applied Research Network
- Study start
- 1 Oct 2026 (estimated)
- Primary completion
- 31 Mar 2031 (estimated)
- Study completion
- 31 Mar 2031 (estimated)
- First posted
- 13 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The TIC-TOC efficacy trial is a multicenter, adaptive allocation, randomized controlled trial of children younger than 18 years with hemorrhagic injuries to the torso and/or brain to evaluate the efficacy of TXA on functional outcome as measured by the PedsQL. Children will be randomized to one of three arms: 1) TXA 15 mg/kg bolus over 30 minutes, followed by a 2 mg/kg/hr infusion over 8 hours), 2) TXA 30 mg/kg bolus over 30 minutes, followed by a 4 mg/kg/hr infusion over 8 hours), and 3) normal saline placebo. A third TXA dose (45 mg/kg bolus dose over 30 minutes, followed by a 6 mg/kg/hr infusion over 8 hours) may be added later in the trial if a dose effect based on accumulating data is noted. The trial will be conducted in the Pediatric Emergency Care Applied Research Network (PECARN) across 40 sites over 4 years of enrollment for a maximum sample size of 2000 patients.
A Bayesian adaptive randomization design will be used to evaluate the efficacy of TXA in children with hemorrhagic brain and/or torso injuries. Because different types of injury have different pathophysiology and potential response to TXA, three different injury strata will be evaluated: isolated hemorrhagic brain injury, isolated hemorrhagic torso injury, and both hemorrhagic brain and torso injuries. The efficacy of TXA will be analyzed across all enrolled children as well as across each type of injury.
The Bayesian adaptive trial design also efficiently evaluates the effectiveness of TXA across different TXA doses. The trial will randomize the first 500 patients to two doses of TXA and placebo at a fixed 1:1:1 ratio. Interim analyses will be conducted when 500, 750, 1000, 1250, 1500, and 1750 patients have been enrolled. At each interim analysis, randomization probabilities will be adjusted in order to preferentially allocate patients to better performing doses, while allocation to the placebo arm will stay fixed. The adaptive randomization will be based entirely on pre-planned rules using accumulating data. A Bayesian hierarchical model will be used to estimate the treatment effect for each of the injury types to be informed by the data accumulated from all injury types. At interim analyses, if a dose effect is noted towards the higher dose of TXA (30 mg/kg bolus then a 4 mg/kg/hr infusion) being more efficacious using pre-specified criteria, then a higher dose study arm (TXA 45 mg/kg bolus then a 6 mg/kg/hr infusion) will be opened later in the trial. If the dose response curve is flat, suggesting that TXA is ineffective, then futility stopping rules can end the trial early.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Bayesian adaptive response
| Arm | Type | Receives |
|---|---|---|
| Tranexamic acid 15 mg/kg bolus | Experimental | Drug: Tranexamic acid injectionSubjects 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. |
| Tranexamic acid 30 mg/kg bolus | Experimental | Drug: Tranexamic acid injectionSubjects 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. |
| Tranexamic acid 45 mg/kg bolus | Experimental | Drug: Tranexamic acid injectionSubjects 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. |
| Placebo | Placebo comparator | Drug: Tranexamic acid injectionSubjects in the placebo group will receive a bolus dose of normal saline over 10 minutes followed by a normal saline infusion over 8 hours |
Who may qualify
- Ages
- 0 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (20 listed)
- Less than 18 years old AND
- Penetrating torso trauma, blunt torso trauma, or head trauma as defined below:
- Penetrating Torso Trauma:
- Blunt Torso Trauma:
- Head Trauma:
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tranexamic acid injectionActive drug is provided to participants as described based on the TXA arm they are randomized to. | Drug | Placebo, Tranexamic acid 15 mg/kg bolus, Tranexamic acid 30 mg/kg bolus, Tranexamic acid 45 mg/kg bolus |
Primary outcome
Pediatric Quality of Life Inventory (PedsQL) area under the curve
Time frame: 1 week, 1 month, 3 months, and 6 months (as measured as an area under the curve)
Neurocognitive functioning and quality-of-life measure; 0 to 100 with higher scores representing better outcomes
3 secondary outcomes
Intracranial hemorrhage progression
Time frame: 24 hours (±6 hours)
Blood transfusion
Time frame: First 48 hours after randomization
PedsQL Physical Domain area under the curve
Time frame: 1 week, 1 month, 3 months, and 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2025.
- Results publication: PubMed 32278572Nishijima 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.
- Results publication: PubMed 31299040Trappey 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.
- Results publication: PubMed 31271691Powers 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.
- TIC-TOC trial websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. A public use database will be produced and will be completely de-identified in accordance with the definitions provided in the Health Insurance Portability and Accountability Act (HIPAA).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel K Nishijima, MD, MAS principal investigator
University of California, Davis
Nathan Kuppermann, MD, MPH principal investigator
University of California, Davis
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tranexamic acid injection in people with Brain Injuries, Traumatic and Wounds and Injury, run by Daniel Nishijima, MD, MAS.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Daniel K Nishijima, MD, MAS (916.734.3884, dnishijima@ucdavis.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pediatric Quality of Life Inventory (PedsQL) area under the curve (time frame: 1 week, 1 month, 3 months, and 6 months (as measured as an area under the curve)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04387305, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2025.