CompletedNCT02840097TIC-TOCUpdated Sep 5, 2021Results posted

Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children: A Pilot and Feasibility Study

A Phase 2 interventional study of Tranexamic Acid and Placebo in Brain Injuries, Wounds and Injuries and Hemorrhage, sponsored by Daniel Nishijima, MD, MAS. Completed at 4 sites in United States. Open to participants aged Up to 17 Years. Per ClinicalTrials.gov, last updated 2021-09-05.

Sponsored by Daniel Nishijima, MD, MAS · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 31
Allocation: Randomized
Ages: Up to 17 Years
Sex: All

Study summary

Trauma is the leading cause of death and disability in children in the United States. The long-term goal of this project is to evaluate the benefits and harms of tranexamic acid (TXA; a drug that stops bleeding) in severely injured children. This is a 40-patient pilot study to evaluate the feasibility of two subsequent large-scale studies of TXA in injured children.

Read the detailed description

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.

Conditions studied

Brain Injuries
Wounds and Injuries
Hemorrhage

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Keywords

Brain injuries
Wounds and injuries
Hemorrhage
Tranexamic acid
Child

In context

Brain Injuries

2,113 studies on the registry are indexed under Brain Injuries; 385 are open to participants now.

This study's enrollment of 31 is below the median of 48 across 1,331 interventional studies indexed under Brain Injuries.

Browse Brain Injuries studies →

Lead sponsor

Daniel Nishijima, MD, MAS is the lead sponsor of 2 studies on the registry; 1 is open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: Up to 17 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

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, 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
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.
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

Exclusion Criteria:

Unable to administer study drug within 3 hours of traumatic event
Known pregnancy
Known prisoners
Known wards 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 bleeding/clotting disorders
Known seizure disorders
Known history of severe renal impairment
Unknown time of injury
Previous enrollment into the TIC-TOC trial
Prior TXA for current injury
Non-English and non-Spanish speaking
Known venous or arterial thrombosis

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 31 participants (actual)

Study arms

Experimental
Tranexamic acid dose A
Subjects will receive a 15 mg/kg bolus of tranexamic acid over 10 minutes followed by a 2mg/kg/h over 8 hours. This represents 31mg/kg total dose of TXA.
Drug: Tranexamic Acid
Experimental
Tranexamic acid dose B
Subjects will receive a 30 mg/kg bolus of tranexamic acid over 10 minutes followed by a 4 mg/kg/h over 8 hours. This represents 62 mg/kg total dose of TXA.
Drug: Tranexamic Acid
Placebo comparator
Placebo
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: Placebo

Interventions

DrugTranexamic Acid
Active drug is provided to participants as described based on the TXA arm they are randomized to.
Also known as: TXA
DrugPlacebo
Normal saline is provided to participants if randomized to this treatment arm.
Also known as: 0.9% Normal Saline

What researchers measure

Primary outcomes

Pediatric Quality of Life Inventory (PedsQL)
Neurocognitive functioning and quality-of-life measures; range from 0 to 100 quality of life units with higher scores representing better outcomes. Measurements occur at 1 week, 1 month, 3 months, and 6 months to generate an area under the curve of quality of life units.
Time frame: 6 months
Pediatric Quality of Life Inventory (PedsQL)
Neurocognitive functioning and quality-of-life measures; range from 0 to 100 with higher scores representing better outcomes
Time frame: 1 week, 1 month, 3 months, and 6 months

Secondary outcomes

Glasgow Outcome Scale-Extended (GOS-E) Peds
Global functioning; range is 1 to 8 with higher scores representing better outcomes; 1=death, 2=vegetative state, 3=lower severe disability, 4=upper severe disability, 5=lower moderate disability, 6=upper moderate disability, 7=lower good recovery, 8=upper good recovery
Time frame: 1 week, 1 month, 3 months, and 6 months
Digit Span Recall Test
Test of working memory; higher scores represent a better outcome, range from 0 to infinity
Time frame: 1 week, 1 month, 3 months, and 6 months
Blood Transfusion
Total volume of packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate
Time frame: First 48 hours after randomization
Intracranial Hemorrhage Progression
Intracranial hemorrhage progression on cranial computed tomography (CT) imaging; hemorrhage will be measured using the ABC/2 volume estimation and relative to the total brain volume (calculated by the XYZ/2 volume estimation); more intracranial hemorrhage progression represents a worse outcome. Change is calculated as the difference between the baseline and repeat cranial CT imaging. The repeat CT is conducted 24 hours (±6 hours) after the baseline CT.
Time frame: 24 hours (±6 hours)
Number of Participants With Any Non-cerebral Venous or Arterial Thrombosis
Any non-cerebral venous or arterial thrombosis on standard diagnostic imaging post-randomization
Time frame: Day 7 of hospitalization or hospital discharge (whichever comes first)
Number of Participants With Seizures
Clinical or electroencephalogram-documented
Time frame: 24 hours after receiving drug
Biomarker Testing
Changes in coagulation biomarkers due to study intervention
Time frame: Baseline and completion of 8 hour infusion

Results

Posted Sep 5, 2021

Participant flow

Participant flow — Overall Study
Milestone	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Started	9	10	12
Completed	9	10	12
Not completed	0	0	0

Outcome measures

PrimaryPediatric Quality of Life Inventory (PedsQL)

Neurocognitive functioning and quality-of-life measures; range from 0 to 100 quality of life units with higher scores representing better outcomes. Measurements occur at 1 week, 1 month, 3 months, and 6 months to generate an area under the curve of quality of life units.

Time frame:: 6 months
Reported as:: Mean · Quality of life units * months

Pediatric Quality of Life Inventory (PedsQL)
Quality of life units * months	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Pediatric Quality of Life Inventory (PedsQL)	64.9 ± 19.0	60.2 ± 12.3	67.2 ± 20.0

PrimaryPediatric Quality of Life Inventory (PedsQL)

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

Time frame:: 1 week, 1 month, 3 months, and 6 months
Reported as:: Mean · units on a scale

Pediatric Quality of Life Inventory (PedsQL)
units on a scale	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
1 week	43.7 ± 24.0	52.4 ± 20.1	57.9 ± 28.6
1 month	57.0 ± 19.8	61.5 ± 16.9	60.5 ± 27.9
3 months	77.3 ± 23.6	77.5 ± 18.5	68.9 ± 22.5
6 months	81.6 ± 23.0	84.3 ± 9.9	68.9 ± 25.9

SecondaryGlasgow Outcome Scale-Extended (GOS-E) Peds

Global functioning; range is 1 to 8 with higher scores representing better outcomes; 1=death, 2=vegetative state, 3=lower severe disability, 4=upper severe disability, 5=lower moderate disability, 6=upper moderate disability, 7=lower good recovery, 8=upper good recovery

Time frame:: 1 week, 1 month, 3 months, and 6 months
Reported as:: Mean · score on a scale

Glasgow Outcome Scale-Extended (GOS-E) Peds
score on a scale	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
1 week	4.6 ± 2.3	5.2 ± 1.8	5.3 ± 2.2
1 month	4.9 ± 2.0	5.1 ± 1.4	4.5 ± 2.2
3 months	3.8 ± 2.3	4.6 ± 1.3	4.2 ± 2.4
6 months	3.7 ± 2.6	2.9 ± 2.3	4.3 ± 2.3

SecondaryDigit Span Recall Test

Test of working memory; higher scores represent a better outcome, range from 0 to infinity

Time frame:: 1 week, 1 month, 3 months, and 6 months
Reported as:: Mean · score on a scale

Digit Span Recall Test
score on a scale	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Total forward digit span, 1 week	8.4 ± 1.7	8.4 ± 4.3	8.8 ± 2.8
Total backward digit span, 1 week	6.0 ± 1.6	6.0 ± 3.3	7.3 ± 1.0
Total forward digit span, 1 month	7.2 ± 1.9	7.9 ± 3.7	7.5 ± 2.6
Total backward digit span, 1 month	6.2 ± 1.8	6.2 ± 1.3	5.3 ± 2.6
Total forward digit span, 3 months	9.1 ± 3.6	10.4 ± 1.5	8.6 ± 2.5
Total backward digit span, 3 months	8.7 ± 3.6	7.8 ± 0.8	6.5 ± 1.1
Total forward digit span, 6 months	11.7 ± 3.9	10.0 ± 2.4	8.4 ± 2.3
Total backward digit span, 6 months	10.4 ± 4.1	6.0 ± 2.4	5.8 ± 2.9

SecondaryBlood Transfusion

Total volume of packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate

Time frame:: First 48 hours after randomization
Reported as:: Mean · ml

Blood Transfusion
ml	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Blood Transfusion	367.4 ± 821.5	150.4 ± 214.1	303.6 ± 571.9

SecondaryIntracranial Hemorrhage Progression

Intracranial hemorrhage progression on cranial computed tomography (CT) imaging; hemorrhage will be measured using the ABC/2 volume estimation and relative to the total brain volume (calculated by the XYZ/2 volume estimation); more intracranial hemorrhage progression represents a worse outcome. Change is calculated as the difference between the baseline and repeat cranial CT imaging. The repeat CT is conducted 24 hours (±6 hours) after the baseline CT.

Time frame:: 24 hours (±6 hours)
Reported as:: Mean · Proportional change

Intracranial Hemorrhage Progression
Proportional change	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Intracranial Hemorrhage Progression	0.003 ± 0.004	0.001 ± 0.001	0.003 ± 0.013

SecondaryNumber of Participants With Any Non-cerebral Venous or Arterial Thrombosis

Any non-cerebral venous or arterial thrombosis on standard diagnostic imaging post-randomization

Time frame:: Day 7 of hospitalization or hospital discharge (whichever comes first)
Reported as:: Count of participants · Participants

Number of Participants With Any Non-cerebral Venous or Arterial Thrombosis
Participants	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Number of Participants With Any Non-cerebral Venous or Arterial Thrombosis	0	0	0

SecondaryNumber of Participants With Seizures

Clinical or electroencephalogram-documented

Time frame:: 24 hours after receiving drug
Reported as:: Count of participants · Participants

Number of Participants With Seizures
Participants	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Number of Participants With Seizures	0	0	1

SecondaryBiomarker Testing

Changes in coagulation biomarkers due to study intervention

Time frame:: Baseline and completion of 8 hour infusion

No measurements were reported for this outcome.

Adverse events

Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Tranexamic Acid Dose A	0/9 (0%)	0/9 (0%)	9/9 (100%)
Tranexamic Acid Dose B	0/10 (0%)	0/10 (0%)	10/10 (100%)
Placebo	0/12 (0%)	1/12 (8.3%)	10/12 (83.3%)

Most frequent serious events

Most frequent serious events
Event	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
SeizureNervous system disorders	0/9	0/10	1/12

Most frequent other events

Most frequent other events
Event	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo
Adverse EventGeneral disorders	9/9	10/10	10/12

Baseline characteristics

Age, Continuous
Age, Continuous(years)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
Mean	12.6 ± 4.4	10.7 ± 4.0	9.2 ± 6.1	10.7 ± 5.0

Sex: Female, Male
Sex: Female, Male(Participants)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
Female	4	2	3	9
Male	5	8	9	22

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
American Indian or Alaska Native	0	0	0	0
Asian	0	0	1	1
Native Hawaiian or Other Pacific Islander	0	0	0	0
Black or African American	2	2	4	8
White	4	6	6	16
More than one race	1	0	0	1
Unknown or Not Reported	2	2	1	5

Injury Type
Injury Type(Participants)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
TBI	4	5	7	16
Torso	5	5	5	15

Method of transport to the emergency department
Method of transport to the emergency department(Participants)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
EMS air	1	4	5	10
EMS ground	8	5	4	17
Private vehicle/walk-in	0	0	1	1
Interfacility transfer	0	0	1	1
Multiple methods of transportation	0	1	1	2

Time from injury to emergency department arrival
Time from injury to emergency department arrival(hours)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
Mean	0.8 ± 0.5	1.2 ± 0.5	1.1 ± 0.8	1.0 ± 0.6

Time from injury to randomization
Time from injury to randomization(hours)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
Mean	2.3 ± 0.5	2.5 ± 0.4	2.4 ± 0.7	2.4 ± 0.6

Primary mechanism of injury
Primary mechanism of injury(Participants)	Tranexamic Acid Dose A	Tranexamic Acid Dose B	Placebo	Total
Fall from greater than standing height	1	2	2	5
MVC	3	4	2	9
Pedestrian/bicyclist hit by moving vehicle	1	0	3	4
Gun-shot wound	2	0	2	4
Recreational vehicle injury	0	1	0	1
Sport-related injury	2	1	2	5
Other	0	2	1	3

16 further baseline measures are reported on the registry.

Study locations

4 sites

University of California, Davis
Sacramento, California 95817, United States
Nationwide Children's Hospital
Columbus, Ohio 43205, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania 19104, United States
Primary Children's Hospital
Salt Lake City, Utah 84113, United States

References and documents

Publications

Nishijima DK, VanBuren J, Hewes HA, Myers SR, Stanley RM, Adelson PD, Barnhard SE, Bobinski M, Ghetti S, Holmes JF, Roberts I, Schalick WO 3rd, Tran NK, Tzimenatos LS, Michael Dean J, Kuppermann N; TIC-TOC Collaborators of the Pediatric Emergency Care Applied Research Network. Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial. Trials. 2018 Oct 30;19(1):593. doi: 10.1186/s13063-018-2974-z. PubMed 30376893 ↗
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 32278572 ↗
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. Erratum In: J Trauma Acute Care Surg. 2022 May 01;92(5):949. doi: 10.1097/01.ta.0000827768.53662.19. PubMed 31299040 ↗
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. PubMed 31271691 ↗
Patel PA, Wyrobek JA, Butwick AJ, Pivalizza EG, Hare GMT, Mazer CD, Goobie SM. Update on Applications and Limitations of Perioperative Tranexamic Acid. Anesth Analg. 2022 Sep 1;135(3):460-473. doi: 10.1213/ANE.0000000000006039. Epub 2022 Aug 17. PubMed 35977357 ↗

Study documents

Protocol and statistical analysis plan · Oct 24, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 5, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02840097
Lead sponsor: Daniel Nishijima, MD, MAS
Collaborators: Pediatric Emergency Care Applied Research Network
Responsible party: Daniel Nishijima, MD, MAS (Associate Professor, Emergency Medicine, University of California, Davis) — Sponsor-investigator
First posted: Jul 21, 2016
Start date: Mar 4, 2019
Primary completion: Oct 3, 2020
Completion: Oct 3, 2020
Results posted: Sep 5, 2021
Last update: Sep 5, 2021

Study contacts

Daniel K Nishijima, MD, MAS

principal investigator · University of California, Davis

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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