PTN timolol study completes patient enrollment

The Pediatric Trials Network (PTN) has enrolled the last patient in its Efficacy, Safety and Pharmacokinetics of Topical Timolol in Infants with Infantile Hemangioma (TIM01) study.

In the study, approximately 110 participants will be randomized to either 0.25% or 0.5% timolol for 180 days to determine the most appropriate dosing level for children younger than three months old.

Timolol is a beta blocker that has increasingly been used for the treatment of Infantile Hemangiomas (IH), commonly called “strawberry” birthmarks, on infants’ skin. The popularity of timolol is likely due to its perceived safety as a topical drug. However, little is known regarding the safety of topical timolol’s use.

To learn more about the PTN timolol study, visit the timolol study page and the timolol highlight on clinicaltrials.gov.

Additional updates will be shared upon the conclusion of the study in 2020.

Rifampin Pharmacokinetics and Safety in Preterm and Term Infants

Antimicrobial Agents and Chemotherapy • May 2019.

Smith PB, Cotten CM, Hudak ML, Sullivan JE, Poindexter BB, Cohen-Wolkowiez M, Boakye-Agyeman F, Lewandowski A, Anand R, Benjamin DK Jr, Laughon MM; Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee.

Rifampin is active against methicillin-resistant staphylococcal species and tuberculosis (TB). We performed a multicenter, prospective pharmacokinetic (PK) and safety study of intravenous rifampin in infants of <121 days postnatal age (PNA). We enrolled 27 infants; the median (range) gestational age was 26 weeks (23 to 41 weeks), and the median PNA was 10 days (0 to 84 days). We collected 102 plasma PK samples from 22 of the infants and analyzed safety data from all 27 infants. We analyzed the data using a population PK approach.

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Systemic Timolol Exposure Following Topical Application to Infantile Hemangiomas

Journal of the American Academy of Dermatology • February 2019.

Drolet BA, Boakye-Agyeman F, Harper B, Holland K, Lewandowski A, Stefanko N, Melloni C; Pediatric Trials Network Steering Committee.

Off-label ophthalmic timolol has been rapidly adopted for treatment of infantile hemangioma since topical application of beta-blockers was presumed to have an improved safety profile compared to oral administration. We examined timolol plasma concentrations in children receiving ophthalmic preparations applied to skin hemangiomas.

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National Survey of Neonatal Intensive Care Unit Medication Safety Practices

American Journal of Perinatology • November 2018.

Greenberg RG, Smith PB, Bose C, Clark RH, Cotten CM, DeRienzo C.

We conducted a detailed survey to identify medication safety practices among a large network of United States neonatal intensive care units (NICUs). We created a 53-question survey to assess 300 U.S. NICU’s demographics, medication safety practices, adverse drug event (ADE) reporting, and ADE response plans.

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Prevalence and safety of diazoxide in the neonatal intensive care unit

Journal of Perinatology • November 2018.

Laughon MM, Benjamin DK Jr, Capparelli EV, Kearns GL, Berezny K, Paul IM, Wade K, Barrett J, Smith PB, Cohen-Wolkowiez M.

Diazoxide is used to treat infants with persistent hypoglycemia, but the prevalence of its use and adverse effects are not well described. We report demographic and clinical characteristics of infants treated with diazoxide in neonatal intensive care units (NICUs).

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Population Pharmacokinetics and Exploratory Exposure-Response Relationships of Diazepam in Children Treated for Status Epilepticus

CPT Pharmacometrics & Systems Pharmacology • November 2018.

Ku LC, Hornik CP, Beechinor RJ, Chamberlain JM, Guptill JT, Harper B, Capparelli EV, Martz K, Anand R, Cohen-Wolkowiez M, Gonzalez D; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

Diazepam is labeled for status epilepticus (SE) in children, but there are limited data characterizing its disposition in pediatric patients. We developed a population pharmacokinetic (PK) model of i.v. diazepam in children with SE. We evaluated relationships between PK parameters and both safety and efficacy, and simulated exposures using dosing regimens from the product label and clinical practice.

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Prolonged furosemide exposure and risk of abnormal newborn hearing screen in premature infants

Early Human Development • October 2018.

Wang LA, Smith PB, Laughon M, Goldberg RN, Ku LC, Zimmerman KO, Balevic S, Clark RH, Benjamin DK, Greenberg RG; Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee.

At very high doses, furosemide is linked to ototoxicity in adults, but little is known about the risk of hearing loss in premature infants exposed to furosemide. Our aim was to evaluate the association between prolonged furosemide exposure and abnormal hearing screening in premature infants.

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A pharmacokinetic model for amiodarone in infants developed from an opportunistic sampling trial and published literature data

Journal of Pharmacokinetics and Pharmacodynamics • June 2018.

Dallefeld SH, Atz AM, Yogev R, Sullivan JE, Al-Uzri A, Mendley SR, Laughon M, Hornik CP, Melloni C, Harper B, Lewandowski A, Mitchell J, Wu H, Green TP, Cohen-Wolkowiez M.

Amiodarone is a first-line antiarrhythmic for life-threatening ventricular fibrillation or ventricular tachycardia in children, yet little is known about its pharmacokinetics (PK) in this population. We developed a population PK (PopPK) model using samples collected via an opportunistic study design of children receiving amiodarone per standard of care supplemented by amiodarone PK data from the literature.

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Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children

The Journal of Clinical Pharmacology • April 2018.

Hornik CP, Gonzalez D, van den Anker J, Atz AM, Yogev R, Poindexter BB, Ng KC, Delmore P, Harper BL, Melloni C, Lewandowski A, Gelber C, Cohen-Wolkowiez M, Lee JH; Pediatric Trial Network Steering Committee.

Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown.

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A Weight Estimation Strategy for Preterm and Full-Term Infants

Global Pediatric Health • December 2017.

Abdel-Rahman SM, Paul IM, Delmore P, James L, Fearn L, Atz A, Poindexter B, Al-Uzri A, Lewandowski A, Harper B, Smith PB.

Weight is the foremost marker of health outcomes in infants; however, the majority of community workers and health care providers in remote, resource-constrained settings have limited access to functional scales. This study develops and validates a simple weight estimation strategy for infants that addresses the limitations of current approaches.

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