Clinical trial NCT02840097: Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children: A Pilot and Feasibility Study
Official title: Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC): A Pilot and Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain Injuries
Wounds and Injuries
Hemorrhage
Keywords: Brain injuries
Wounds and injuries
Hemorrhage
Tranexamic acid
Child
Lead sponsor: University of California, Davis
Sponsor class: OTHER
Collaborators: name: Pediatric Emergency Care Applied Research Network
First posted: 2016-07-21
Enrollment: 31
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Pediatric Quality of Life Inventory (PedsQL)
timeFrame: 6 months
measure: Pediatric Quality of Life Inventory (PedsQL)
timeFrame: 1 week, 1 month, 3 months, and 6 months
Secondary outcomes:
measure: Glasgow Outcome Scale-Extended (GOS-E) Peds
timeFrame: 1 week, 1 month, 3 months, and 6 months
measure: Digit Span Recall Test
timeFrame: 1 week, 1 month, 3 months, and 6 months
measure: Blood Transfusion
timeFrame: First 48 hours after randomization
measure: Intracranial Hemorrhage Progression
timeFrame: 24 hours (±6 hours)
measure: Number of Participants With Any Non-cerebral Venous or Arterial Thrombosis
timeFrame: Day 7 of hospitalization or hospital discharge (whichever comes first)
measure: Number of Participants With Seizures
timeFrame: 24 hours after receiving drug
measure: Biomarker Testing
timeFrame: Baseline and completion of 8 hour infusion
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Salt Lake City
country: United States
facility: Primary Children's Hospital
state: Utah
Study officials:
affiliation: University of California, Davis
name: Daniel K Nishijima, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References:
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 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.
citation: 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.
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 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.
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: 10.1111/acem.13827. Epub 2019 Jul 24.
citation: 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.