Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Pediatric Emergency Care Applied Research Network | NETWORK |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tranexamic acid dose A | Experimental | 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. |
|
| Tranexamic acid dose B | Experimental | 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. |
|
| Placebo | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tranexamic Acid | Drug | Active drug is provided to participants as described based on the TXA arm they are randomized to. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
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:
Blunt Torso Trauma (at least one of the following):
Clinician suspicion of hemorrhagic blunt torso injury and at least one of the following:
Hemothorax on chest tube placement or imaging,
Clinical suspicion of hemorrhagic blunt torso injury and Intraperitoneal fluid on abdominal ultrasonography (Focused Assessment with Sonography in Trauma),
Intra-abdominal injury on CT with either contrast extravasation or more than trace intraperitoneal fluid,
Pelvic fracture with contrast extravasation or hematoma on abdominal/pelvic CT scan with at least one of the following:
Head Trauma:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Daniel K Nishijima, MD, MAS | University of California, Davis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, Davis | Sacramento | California | 95817 | United States | ||
| Nationwide Children's Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30376893 | Result | 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. | |
| 32278572 |
| Label | URL |
|---|---|
| TIC-TOC trial website | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. Tranexamic Acid: Active drug is provided to participants as described based on the TXA arm they are randomized to. |
| FG001 | 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. Tranexamic Acid: Active drug is provided to participants as described based on the TXA arm they are randomized to. |
| FG002 | 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. Placebo: Normal saline is provided to participants if randomized to this treatment arm. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. Tranexamic Acid: Active drug is provided to participants as described based on the TXA arm they are randomized to. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | Quality of life units * months | 6 months |
|
6 months
Adverse Events were monitored/assessed without regard to the specific Adverse Event; defined as any untoward medical occurrence experienced by a subject; may constitute a disease, a set of related signs or symptoms, or a single sign or symptom
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Tranexamic Acid: Active drug is provided to participants as described based on the TXA arm they are randomized to. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Seizure | Nervous system disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Adverse Event | General disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daniel Nishijima, Study Co-PI | University of California, Davis | 916.734.3884 | dnishijima@ucdavis.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 24, 2018 | Jul 6, 2021 | Prot_SAP_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D014947 | Wounds and Injuries |
| D006470 | Hemorrhage |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D006259 | Craniocerebral Trauma |
Not provided
Not provided
| ID | Term |
|---|---|
| D014148 | Tranexamic Acid |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D003509 | Cyclohexanecarboxylic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | Normal saline is provided to participants if randomized to this treatment arm. |
|
|
| 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 |
| Blood Transfusion | Total volume of packed red blood cells, platelets, fresh frozen plasma, and cryoprecipitate | 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. | 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 | Day 7 of hospitalization or hospital discharge (whichever comes first) |
| Number of Participants With Seizures | Clinical or electroencephalogram-documented | 24 hours after receiving drug |
| Biomarker Testing | Changes in coagulation biomarkers due to study intervention | Baseline and completion of 8 hour infusion |
| 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 |
| Result |
| 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. |
| 31299040 | Result | 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. |
| 31271691 | Result | 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. |
| 35977357 | Derived | 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. |
| 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. Tranexamic Acid: Active drug is provided to participants as described based on the TXA arm they are randomized to. |
| BG002 | 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. Placebo: Normal saline is provided to participants if randomized to this treatment arm. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Injury Type | Count of Participants | Participants |
|
| Method of transport to the emergency department | Count of Participants | Participants |
|
| Time from injury to emergency department arrival | Mean | Standard Deviation | hours |
|
| Time from injury to randomization | Mean | Standard Deviation | hours |
|
| Primary mechanism of injury | Count of Participants | Participants |
|
| Initial Glasgow Coma Scale score (3 to 15) | Scale is 3 to 15; lower scores represent more severe traumatic brain injury | Median | Inter-Quartile Range | units on a scale |
|
| Emergency department disposition | Count of Participants | Participants |
|
| Patient received craniotomy or craniectomy | Count of Participants | Participants |
|
| Patient received an intracranial pressure monitor | Count of Participants | Participants |
|
| Patient received a laparotomy | Count of Participants | Participants |
|
| Patient received a thoracotomy | Count of Participants | Participants |
|
| Length of hospitalization | Mean | Standard Deviation | days |
|
| Injury Severity Scale score (0 to 75) | Scale is 0 to 75 with higher scores representing more severe injury | Mean | Standard Deviation | units on a scale |
|
| Presence of peritoneal free fluid on initial focused assessment with sonography for trauma exam | Count of Participants | Participants |
|
| pH | Mean | Standard Deviation | units on a scale |
|
| Serum bicarbonate | Mean | Standard Deviation | mmol/L |
|
| Creatinine | Mean | Standard Deviation | mg/dL |
|
| International Normalized Ratio | Normal range is 0.8 to 1.1 | Mean | Standard Deviation | ratio |
|
| Hemoglobin | Mean | Standard Deviation | g/dL |
|
| Platelets | Mean | Standard Deviation | platelets per microliter |
|
| Glomerular filtration rate () | Count of Participants | Participants |
|
| OG002 | 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. |
|
|
| 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 | Posted | Mean | Standard Deviation | units on a scale | 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 | Posted | Mean | Standard Deviation | score on a scale | 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 | Posted | Mean | Standard Deviation | score on a scale | 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 | Torso and Both groups | Posted | Mean | Standard Deviation | ml | 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. | Brain Injury and Both groups | Posted | Mean | Standard Deviation | Proportional change | 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 | Posted | Count of Participants | Participants | Day 7 of hospitalization or hospital discharge (whichever comes first) |
|
|
|
| Secondary | Number of Participants With Seizures | Clinical or electroencephalogram-documented | Posted | Count of Participants | Participants | 24 hours after receiving drug |
|
|
|
| Secondary | Biomarker Testing | Changes in coagulation biomarkers due to study intervention | Data were not collected | Posted | Baseline and completion of 8 hour infusion |
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| 9 |
| 9 |
| EG001 | 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. Tranexamic Acid: Active drug is provided to participants as described based on the TXA arm they are randomized to. | 0 | 10 | 0 | 10 | 10 | 10 |
| EG002 | 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. Placebo: Normal saline is provided to participants if randomized to this treatment arm. | 0 | 12 | 1 | 12 | 10 | 12 |
Not provided
Not provided
| D020196 | Trauma, Nervous System |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000077324 |
| Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
|
| 3 months |
|
| 6 months |
|
|
| 3 months |
|
| 6 months |
|
|
| Total forward digit span, 1 month |
|
| Total backward digit span, 1 month |
|
| Total forward digit span, 3 months |
|
| Total backward digit span, 3 months |
|
| Total forward digit span, 6 months |
|
| Total backward digit span, 6 months |
|