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Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC)

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ClinicalTrials.gov Identifier: NCT02840097
Recruitment Status : Recruiting
First Posted : July 21, 2016
Last Update Posted : April 17, 2019
Sponsor:
Collaborator:
Pediatric Emergency Care Applied Research Network
Information provided by (Responsible Party):
Daniel Nishijima, MD, University of California, Davis

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.

Condition or disease Intervention/treatment Phase
Brain Injuries Wounds and Injuries Hemorrhage Drug: Tranexamic Acid Drug: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC): A Pilot and Feasibility Study
Actual Study Start Date : March 4, 2019
Estimated Primary Completion Date : June 2020
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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
Active drug is provided to participants as described based on the TXA arm they are randomized to.
Other Name: TXA

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

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
Normal saline is provided to participants if randomized to this treatment arm.
Other Name: 0.9% Normal Saline




Primary Outcome Measures :
  1. Pediatric Quality of Life Inventory (PedsQL) [ Time Frame: 1 week, 1 month, 3 months, and 6 months ]
    Neurocognitive functioning and quality-of-life measures


Secondary Outcome Measures :
  1. Glasgow Outcome Scale-Extended (GOS-E) Peds [ Time Frame: 1 week, 1 month, 3 months, and 6 months ]
    Global functioning

  2. Digit span recall test [ Time Frame: 1 week, 1 month, 3 months, and 6 months ]
    Test of working memory

  3. Blood transfusion [ Time Frame: First 48 hours after randomization ]
    Total volume of packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate

  4. Intracranial hemorrhage progression [ Time Frame: 24 hours (±6 hours) ]
    Intracranial hemorrhage progression on cranial computed tomography imaging

  5. Venothromboembolic disease [ Time Frame: Day 7 of hospitalization or hospital discharge (whichever comes first) ]
    Any non-cerebral venous or arterial thrombosis on standard diagnostic imaging post-randomization

  6. Seizures [ Time Frame: 24 hours after receiving drug ]
    Clinical or electroencephalogram-documented

  7. Biomarker testing [ Time Frame: Baseline and completion of 8 hour infusion ]
    Changes in coagulation biomarkers due to study intervention



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. Suspected non-accidental trauma (child abuse)
  12. Unknown time of injury
  13. Previous enrollment into the TIC-TOC trial
  14. Prior TXA for current injury
  15. Non-English and non-Spanish speaking
  16. Known venous or arterial thrombosis

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02840097


Contacts
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Contact: Daniel K Nishijima, MD, MAS 9167343884 dnishijima@ucdavis.edu
Contact: Nathan Kuppermann, MD, MPH 9167341535 nkuppermann@ucdavis.edu

Locations
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United States, California
University of California, Davis Not yet recruiting
Sacramento, California, United States, 95817
Contact: Cindy Valencia    916-734-0373    cvvalencia@ucdavis.edu   
Contact: Kyle Pimenta    9167348847    kpimenta@ucdavis.edu   
Principal Investigator: Nathan Kuppermann, MD, MPH         
Principal Investigator: Daniel K Nishijima, MD, MAS         
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Rachel M Stanley, MD    614-722-4384    Rachel.Stanley@nationwidechildrens.org   
Principal Investigator: Rachel M Stanley, MD         
United States, Pennsylvania
Children's Hospital of Philadelphia Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Sage Myers, MD, MSCE       myerss@email.chop.edu   
Principal Investigator: Sage Myers, MD         
United States, Utah
Primary Children's Hospital Recruiting
Salt Lake City, Utah, United States, 84113
Contact: Hilary A Hewes, MD    801-662-1000    Hilary.Hewes@hsc.utah.edu   
Principal Investigator: Hilary A Hewes, MD         
Sponsors and Collaborators
Daniel Nishijima, MD
Pediatric Emergency Care Applied Research Network
Investigators
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Principal Investigator: Daniel K Nishijima, MD, MAS University of California, Davis

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Daniel Nishijima, MD, Associate Professor, Emergency Medicine, University of California, Davis
ClinicalTrials.gov Identifier: NCT02840097     History of Changes
Other Study ID Numbers: 1023599
First Posted: July 21, 2016    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Daniel Nishijima, MD, University of California, Davis:
Brain injuries
Wounds and injuries
Hemorrhage
Tranexamic acid
Child

Additional relevant MeSH terms:
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Wounds and Injuries
Brain Injuries
Hemorrhage
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Pathologic Processes
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants