Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): a pilot randomized trial.

2022

2022 Mar 10

1553-2712

<p><strong>BACKGROUND: </strong>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 evaluated the feasibility of a large-scale trial evaluating the effects of TXA in children with severe hemorrhagic injuries.</p>

<p><strong>METHODS: </strong>Severely injured children (0 up to 18 birthday) were randomized into a double-blind randomized trial of 1) TXA 15 mg/kg bolus dose, followed by 2 mg/kg/hr infusion over 8 hours, 2) TXA 30 mg/kg bolus dose, followed by 4 mg/kg/hr infusion over 8 hours, or 3) normal saline placebo bolus and infusion. The trial was conducted at 4 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.</p>

<p><strong>RESULTS: </strong>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 hours (SD 0.6 hours). 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 (9 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.</p>

<p><strong>CONCLUSION: </strong>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.</p>

10.1111/acem.14481

Acad Emerg Med

35266589

PRagMatic Pediatric Trial of Balanced versus nOrmaL Saline FlUid in Sepsis: the PRoMPT BOLUS Randomized Controlled Trial Pilot Feasibility Study.

2019

2019 Jun 10

1553-2712

<p><strong>BACKGROUND: </strong>Resuscitation with crystalloid fluid is a cornerstone of pediatric septic shock treatment. However, the optimal type of crystalloid fluid is unknown. We aimed to determine the feasibility of conducting a pragmatic randomized trial to compare balanced (lactated Ringer's [LR]) with 0.9% normal saline (NS) fluid resuscitation in children with suspected septic shock.</p>

<p><strong>METHODS: </strong>Open-label pragmatic randomized controlled trial (RCT) at a single academic children's hospital from January - August 2018. Eligible patients were &gt;6 months to &lt;18 years-old who were treated in the emergency department for suspected septic shock, operationalized as blood culture, parenteral antibiotics, and fluid resuscitation for abnormal perfusion. Screening, enrollment, and randomization were carried out by the clinical team as part of routine care. Patients were randomized to receive either LR or NS for up to 48 hours following randomization. Other than fluid type, all treatment decisions were at the clinical team's discretion. Feasibility outcomes included proportion of eligible patients enrolled, acceptability of enrollment via the U.S. federal exception from informed consent (EFIC) regulations, and adherence to randomized study fluid administration.</p>

<p><strong>RESULTS: </strong>Of 59 eligible patients, 50 (85%) were enrolled and randomized. Twenty four were randomized to LR and 26 to NS. Only one (2%) of 44 patients enrolled using EFIC withdrew before study completion. Total median crystalloid fluid volume received during the intervention window was 107 (IQR 60, 155) mL/kg and 98 (IQR 63, 128) mL/kg in the LR and NS arms, respectively (p=0.50). Patients randomized to LR received a median of only 20% (IQR 13, 32) of all study fluid as NS compared to 99% (IQR 64,100%) of study fluid as NS in the NS arm (absolute difference 79%, 95% CI 48,85).</p>

<p><strong>CONCLUSIONS: </strong>A pragmatic study design proved feasible to study comparative effectiveness of LR versus NS fluid resuscitation for pediatric septic shock. This article is protected by copyright. All rights reserved.</p>

10.1111/acem.13815

Acad Emerg Med

31183919

Traumatic injury clinical trial evaluating tranexamic acid in children (TIC-TOC): study protocol for a pilot randomized controlled trial.

2018

593

2018 Oct 30

1745-6215

<p><strong>BACKGROUND: </strong>Trauma is the leading cause of morbidity and mortality in children in the United States. The antifibrinolytic drug tranexamic acid (TXA) improves survival in adults with traumatic hemorrhage, however, the drug has not been evaluated in a clinical trial in severely injured children. We designed the Traumatic Injury Clinical Trial Evaluating Tranexamic Acid in Children (TIC-TOC) trial to evaluate the feasibility of conducting a confirmatory clinical trial that evaluates the effects of TXA in children with severe trauma and hemorrhagic injuries.</p>

<p><strong>METHODS: </strong>Children with severe trauma and evidence of hemorrhagic torso or brain injuries will be randomized to one of three arms: (1) TXA dose A (15&nbsp;mg/kg bolus dose over 20&nbsp;min, followed by 2&nbsp;mg/kg/hr infusion over 8&nbsp;h), (2) TXA dose B (30&nbsp;mg/kg bolus dose over 20&nbsp;min, followed by 4&nbsp;mg/kg/hr infusion over 8&nbsp;h), or (3) placebo. We will use permuted-block randomization by injury type: hemorrhagic brain injury, hemorrhagic torso injury, and combined hemorrhagic brain and torso injury. The trial will be conducted at four pediatric Level I trauma centers. We will collect the following outcome measures: global functioning as measured by the Pediatric Quality of Life (PedsQL) and Pediatric Glasgow Outcome Scale Extended (GOS-E Peds), working memory (digit span test), total amount of blood products transfused in the initial 48&nbsp;h, intracranial hemorrhage progression at 24&nbsp;h, coagulation biomarkers, and adverse events (specifically thromboembolic events and seizures).</p>

<p><strong>DISCUSSION: </strong>This multicenter trial will provide important preliminary data and assess the feasibility of conducting a confirmatory clinical trial that evaluates the benefits of TXA in children with severe trauma and hemorrhagic injuries to the torso and/or brain.</p>

<p><strong>TRIAL REGISTRATION: </strong>ClinicalTrials.gov registration number: NCT02840097 . Registered on 14 July 2016.</p>

10.1186/s13063-018-2974-z

Trials

30376893

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

2018

2275-2287

2018 06 14

1533-4406

<p><strong>BACKGROUND: </strong>Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades.</p>

<p><strong>METHODS: </strong>We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of &lt;14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis.</p>

<p><strong>RESULTS: </strong>A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups.</p>

<p><strong>CONCLUSIONS: </strong>Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).</p>

10.1056/NEJMoa1716816

N. Engl. J. Med.

29897851

The Pediatric Emergency Care Applied Research Network Registry: A Multicenter Electronic Health Record Registry of Pediatric Emergency Care.

2018

366-376

2018 Apr

1869-0327

<p><strong>BACKGROUND: </strong> Electronic health record (EHR)-based registries allow for robust data to be derived directly from the patient clinical record and can provide important information about processes of care delivery and patient health outcomes.</p>

<p><strong>METHODS: </strong> A data dictionary, and subsequent data model, were developed describing EHR data sources to include all processes of care within the emergency department (ED). ED visit data were deidentified and XML files were created and submitted to a central data coordinating center for inclusion in the registry. Automated data quality control occurred prior to submission through an application created for this project. Data quality reports were created for manual data quality review.</p>

<p><strong>RESULTS: </strong> The Pediatric Emergency Care Applied Research Network (PECARN) Registry, representing four hospital systems and seven EDs, demonstrates that ED data from disparate health systems and EHR vendors can be harmonized for use in a single registry with a common data model. The current PECARN Registry represents data from 2,019,461 pediatric ED visits, 894,503 distinct patients, more than 12.5 million narrative reports, and 12,469,754 laboratory tests and continues to accrue data monthly.</p>

<p><strong>CONCLUSION: </strong> The Registry is a robust harmonized clinical registry that includes data from diverse patients, sites, and EHR vendors derived via data extraction, deidentification, and secure submission to a central data coordinating center. The data provided may be used for benchmarking, clinical quality improvement, and comparative effectiveness research.</p>

10.1055/s-0038-1651496

Appl Clin Inform

29791930