Assessment of primary outcome measures for a clinical trial of pediatric hemorrhagic injuries

Nishijima, Daniel K.; Gosdin, Melissa; Naz, Hiba; Tancredi, Daniel J.; Hewes, Hilary A; Myers, Sage; Stanley, Rachel; Adelson, P. David; Burd, Randall S.; Finkelstein, Yaron; VanBuren, John M.; Casper, T. Charles; Kuppermann, Nathan

doi:10.1016/j.ajem.2020.03.001

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…Although the trial was not powered to evaluate the efficacy of clinical outcomes, we collected the following outcomes: the Pediatric Quality of Life Inventory (PedsQL; primary clinical outcome; measure of global functioning), the Pediatric Glasgow Outcome Scale—Extended (GOS‐E Peds; global functioning), digit span recall (a test of working memory for children 3 years and older), total blood products (ml/kg) transfused over the initial 48 h of care (for children with torso injuries), intracranial hemorrhage progression in first 24 h (for children with brain injuries), and adverse events. The PedsQL will be the primary outcome measure for the phase 3 trial and is a well‐validated measure of global functioning in preverbal and verbal children 32 . The PedsQL, GOS‐E Peds, and digit span recall were measured 1 week, 1 month, 3 months, and 6 months after ED presentation for all enrolled children.…”

Section: Methodsmentioning

confidence: 99%

“…The PedsQL will be the primary outcome measure for the phase 3 trial and is a well-validated measure of global functioning in preverbal and verbal children. 32 The PedsQL, GOS-E Peds, and digit span recall were measured 1 week, 1 month, 3 months, and 6 months after ED presentation for all enrolled children. Blood product transfusion volume was calculated as the total mL/kg blood products received from randomization to 48 h after randomization.…”

Section: Clinical Outcomesmentioning

confidence: 99%

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Traumatic injury clinical trial evaluating tranexamic acid in children (TIC‐TOC): A pilot randomized trial

Nishijima

VanBuren

Linakis

et al. 2022

Academic Emergency Medicine

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Background The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage; however, the drug has not been evaluated in a trial in injured children. We assessed the feasibility of a large‐scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries. Methods Severely injured children (0 up to 18th birthday) were randomized into a double‐blind randomized trial of (1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/h infusion over 8 h, (2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/h infusion over 8 h, or (3) normal saline placebo bolus and infusion. The trial was conducted at four pediatric Level I trauma centers in the United States between June 2018 and March 2020. We enrolled patients under federal exception from informed consent (EFIC) procedures when parents were unable to provide informed consent. Feasibility outcomes included the rate of enrollment, adherence to intervention arms, and ability to measure the primary clinical outcome. Clinical outcomes included global functioning (primary), working memory, total amount of blood products transfused, intracranial hemorrhage progression, and adverse events. The target enrollment rate was at least 1.25 patients per site per month. Results A total of 31 patients were randomized with a mean age of 10.7 years (standard deviation [SD] 5.0 years) and 22 (71%) patients were male. The mean time from injury to randomization was 2.4 h (SD 0.6 h). Sixteen (52%) patients had isolated brain injuries and 15 (48%) patients had isolated torso injuries. The enrollment rate using EFIC was 1.34 patients per site per month. All eligible enrolled patients received study intervention (nine patients TXA 15 mg/kg bolus dose, 10 patients TXA 30 mg/kg bolus dose, and 12 patients placebo) and had the primary outcome measured. No statistically significant differences in any of the clinical outcomes were identified. Conclusion Based on enrollment rate, protocol adherence, and measurement of the primary outcome in this pilot trial, we confirmed the feasibility of conducting a large‐scale, randomized trial evaluating the efficacy of TXA in severely injured children with hemorrhagic brain and/or torso injuries using EFIC.

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Section: Methodsmentioning

confidence: 99%

Section: Clinical Outcomesmentioning

confidence: 99%

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC‐TOC): A pilot randomized trial

Nishijima

VanBuren

Linakis

et al. 2022

Academic Emergency Medicine

Self Cite

View full text Add to dashboard Cite

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The design of a Bayesian adaptive clinical trial of tranexamic acid in severely injured children

VanBuren

Casper

Nishijima

et al. 2021

Trials

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Background Trauma is the leading cause of death and disability in children in the USA. Tranexamic acid (TXA) reduces the blood transfusion requirements in adults and children during surgery. Several studies have evaluated TXA in adults with hemorrhagic trauma, but no randomized controlled trials have occurred in children with trauma. We propose a Bayesian adaptive clinical trial to investigate TXA in children with brain and/or torso hemorrhagic trauma. Methods/design We designed a double-blind, Bayesian adaptive clinical trial that will enroll up to 2000 patients. We extend the traditional Emax dose-response model to incorporate a hierarchical structure so multiple doses of TXA can be evaluated in different injury populations (isolated head injury, isolated torso injury, or both head and torso injury). Up to 3 doses of TXA (15 mg/kg, 30 mg/kg, and 45 mg/kg bolus doses) will be compared to placebo. Equal allocation between placebo, 15 mg/kg, and 30 mg/kg will be used for an initial period within each injury group. Depending on the dose-response curve, the 45 mg/kg arm may open in an injury group if there is a trend towards increasing efficacy based on the observed relationship using the data from the lower doses. Response-adaptive randomization allows each injury group to differ in allocation proportions of TXA so an optimal dose can be identified for each injury group. Frequent interim stopping periods are included to evaluate efficacy and futility. The statistical design is evaluated through extensive simulations to determine the operating characteristics in several plausible scenarios. This trial achieves adequate power in each injury group. Discussion This trial design evaluating TXA in pediatric hemorrhagic trauma allows for three separate injury populations to be analyzed and compared within a single study framework. Individual conclusions regarding optimal dosing of TXA can be made within each injury group. Identifying the optimal dose of TXA, if any, for various injury types in childhood may reduce death and disability.

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Assessment of primary outcome measures for a clinical trial of pediatric hemorrhagic injuries

Cited by 2 publications

References 27 publications

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC‐TOC): A pilot randomized trial

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC‐TOC): A pilot randomized trial

The design of a Bayesian adaptive clinical trial of tranexamic acid in severely injured children

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