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

NCT ID: NCT02840097

Last Updated: 2021-09-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-04
• Study Completion Date: 2020-10-03

Brief 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.

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

Brain Injuries; Wounds and Injuries; Hemorrhage

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Tranexamic Acid

Intervention Type: DRUG

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

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.

Group Type: EXPERIMENTAL

Tranexamic Acid

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline is provided to participants if randomized to this treatment arm.

Interventions

Tranexamic Acid

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

Intervention Type: DRUG

Placebo

Normal saline is provided to participants if randomized to this treatment arm.

Intervention Type: DRUG

Other Intervention Names

TXA; 0.9% Normal Saline

Eligibility Criteria

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

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pediatric Emergency Care Applied Research Network

NETWORK

Sponsor Role: collaborator

Daniel Nishijima, MD, MAS

OTHER

Sponsor Role: lead

Responsible Party

Daniel Nishijima, MD, MAS

Associate Professor, Emergency Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Daniel K Nishijima, MD, MAS

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California, Davis

Sacramento, California, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 30376893 (View on PubMed)

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.

Reference Type: RESULT

PMID: 32278572 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31299040 (View on PubMed)

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.

Reference Type: RESULT

PMID: 31271691 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35977357 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://tictoctrial.org/

TIC-TOC trial website

Other Identifiers

1023599

Identifier Type: -

Identifier Source: org_study_id