Read the 2022 PTN Annual Review.
This PTN Annual Review summarizes the Network’s activities in 2022.
Author: Kayla Korzekwinski
PPE Results-at-a-Glance
Read PPE Results-at-a-Glance summary.
Personal protective equipment (PPE) is worn by health care providers to protect them from exposure to hazardous materials such as chemicals or infectious diseases. Previous studies examining the effects of PPE on health care providers’ ability to perform emergency tasks have had mixed results. Additionally, there have not been studies evaluating the performance of these tasks on children while wearing PPE. These studies were needed to determine how PPE impacts health care providers’ ability to perform emergency care for pediatric groups.
Use of Real-World Data and Physiologically-Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity
Clinical Pharmacology & Therapeutics • August 2022
Gerhart JG, Carreño FO, Loop MS, Lee CR, Edginton AN, Sinha J, Kumar KR, Kirkpatrick CM, Hornik CP, Gonzalez D; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Dosing guidance for children with obesity is often unknown despite the fact that nearly 20% of US children are classified as obese. Enoxaparin, a commonly prescribed low-molecular-weight heparin, is dosed based on body weight irrespective of obesity status to achieve maximum concentration within a narrow therapeutic or prophylactic target range. However, whether children with and without obesity experience equivalent enoxaparin exposure remains unclear. The study aimed to answer this clinical question. Enoxaparin exposure was better matched across age groups and obesity status using fat-free mass weight-based dosing.
Exposure-safety relationship for acyclovir in the treatment of neonatal herpes simplex virus disease
Early Human Development • July 2022
Ericson J, Benjamin DK Jr., Boakye-Agyeman F, Balevic SJ, Cotten MC, Adler-Shohet F, Laughon M, Poindexter B, Harper B, Payne EH, Kaneshige K, Smith PB; Best Pharmaceuticals for Children Act – Pediatric Trials Network
Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991. This study aimed to determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir and examine the association between acyclovir dose and exposure with adverse events (AEs). The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure. Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.
Population Pharmacokinetics of Piperacillin/Tazobactam Across the Adult Lifespan
Clinical Pharmacokinetics • January 2023
Hemmersbach-Miller M, Balevic SJ, Winokur PL, Landersdorfer C, Gu K, Chan AW, Cohen-Wolkowiez M, Conrad T, An G, Kirkpatrick C, Swamy GK, Walter EB, Schmader KE
Piperacillin/tazobactam is one of the most frequently used antimicrobials in older adults. Using an opportunistic study design, we evaluated the pharmacokinetics of piperacillin/tazobactam as a probe drug to evaluate changes in antibacterial drug exposure and dosing requirements, including in older adults.
Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response
Journal of Clinical Pharmacology • January 2023
Balevic SJ, Niu J, Chen J, Green D, McMahon A, Hornik CP, Schanberg L, Glaser R, Doddapaneni S, Gonzalez D, Burckart GJ
To streamline drug development, the United States Food and Drug Administration (FDA) can consider the extrapolation of adult efficacy data to children when the disease and drug effects are sufficiently similar. This study explored whether the relationship between drug exposure and response for selected drugs in systemic lupus erythematosus (SLE) was sufficiently similar to support a consideration of the extrapolation of adult efficacy data to children of ≥5 years of age.
Methylprednisolone for Heart Surgery in Infants – A Randomized, Controlled Trial
The New England Journal of Medicine • December 2022
Hill KD, Kannankeril PJ, Jacobs JP, Baldwin HS, Jacobs ML, O’Brien SM, Bichel DP, Graham EM, Blasiole B, Resheidat A, Husain AS, Kumar SR, Kirchner JL, Gallup DS, Turek JW, Bleiweis M, Mettler B, Benscoter A, Wald E, Karamlou T, Van Bergen AH, Overman D
Although perioperative prophylactic glucocorticoids have been used for decades, whether they improve outcomes in infants after heart surgery with cardiopulmonary bypass is unknown. This study was a multicenter, prospective, randomized, placebo-controlled, registry-based trial involving infants (<1 year of age) undergoing heart surgery with cardiopulmonary bypass at 24 sites participating in the Society of Thoracic Surgeons Congenital Heart Surgery Database.
Ampicillin dosing in premature infants for early-onset sepsis: exposure-driven efficacy, safety, and stewardship
Journal of Perinatology • July 2022
Le J, Greenberg RG, Yoo Y, Clark RH, Benjamin DK Jr., Zimmerman KO, Cohen-Wolkowiez M, Wade K
This study simulated ampicillin concentrations in newborns to define optimal ampicillin dosing for empiric early-onset sepsis (EOS) therapy in preterm neonates. For EOS in preterm infants, two ampicillin doses (50 mg/kg) provided optimal bactericidal exposures, while minimizing potential toxicity.
Developing lay summaries and thank you notes in paediatric pragmatic clinical trials
Health Expectations • June 2022
Zimmerman KO, Perry B, Nsonwu A, Hanlen-Rosado E, Lane MD, Benjamin DK Jr., Becker M, Corneli A; on behalf of the Best Pharmaceuticals for Children Act — Pediatric Trials Network Steering Committee
This study conducted formative research to assess the acceptability of lay summaries and thank you notes, as well as to refine and expand guidance on participant and family engagement in Pediatric Trials Network’s (PTN) pragmatic paediatric clinical research. Researchers conducted in-depth qualitative interviews with adolescent clinical trial participants and caregivers of paediatric participants in four trials conducted by PTN across eight sites. This is the first study to describe stakeholder preferences for thank you note content and layout. Using these findings, researchers finalized PTN’s trial communication guidance for use in future PTN trials.
Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity
CPT: Pharmacometrics & Systems Pharmacology • June 2022
Gerhart JG, Carreno FO, Ford JL, Edginton AN, Perrin EM, Watt KM, Muller WJ, Atz AM, Al-Uzri A, Delmore P, Gonzalez D; on behalf of the Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reducing the risk of serious adverse events associated with overexposure. However, there is limited information to guide fentanyl and methadone dosing in these children. This study addresses the clinical knowledge gap using physiologically-based pharmacokinetic models of fentanyl and methadone developed in adults and scaled to children with and without obesity to explore the interplay of obesity, age, and pharmacogenomics.