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

Brain Injuries Clinical Trial

— TIC-TOC  

Official title:

Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC): A Pilot and Feasibility Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02840097
• Other study ID #: 1023599
• Status: Completed
• Phase: Phase 2
• Start date: March 4, 2019
• Est. completion date: October 3, 2020

Study information

• Verified date: September 2021
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: October 3, 2020
• Est. primary completion date: October 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 17 Years

Eligibility

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. Unknown time of injury

12. Previous enrollment into the TIC-TOC trial

13. Prior TXA for current injury

14. Non-English and non-Spanish speaking

15. Known venous or arterial thrombosis

Related Conditions & MeSH terms

• Brain Injuries
• Hemorrhage
• Wounds and Injuries

Intervention

Drug:
• Tranexamic Acid
Active drug is provided to participants as described based on the TXA arm they are randomized to.
• Placebo
Normal saline is provided to participants if randomized to this treatment arm.

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of California, Davis	Sacramento	California
United States	Primary Children's Hospital	Salt Lake City	Utah

Sponsors (2)

Lead Sponsor	Collaborator
Daniel Nishijima, MD, MAS	Pediatric Emergency Care Applied Research Network

Country where clinical trial is conducted

United States, 

References & Publications (4)

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 pri — View Citation

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 App — View Citation

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: — View Citation

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 Ap — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 months
Primary	Pediatric Quality of Life Inventory (PedsQL)	Neurocognitive functioning and quality-of-life measures; range from 0 to 100 with higher scores representing better outcomes	1 week, 1 month, 3 months, and 6 months
Secondary	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	1 week, 1 month, 3 months, and 6 months
Secondary	Digit Span Recall Test	Test of working memory; higher scores represent a better outcome, range from 0 to infinity	1 week, 1 month, 3 months, and 6 months
Secondary	Blood Transfusion	Total volume of packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate	First 48 hours after randomization
Secondary	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.	24 hours (±6 hours)
Secondary	Number of Participants With Any Non-cerebral Venous or Arterial Thrombosis	Any non-cerebral venous or arterial thrombosis on standard diagnostic imaging post-randomization	Day 7 of hospitalization or hospital discharge (whichever comes first)
Secondary	Number of Participants With Seizures	Clinical or electroencephalogram-documented	24 hours after receiving drug
Secondary	Biomarker Testing	Changes in coagulation biomarkers due to study intervention	Baseline and completion of 8 hour infusion

External Links

•   TIC-TOC trial website