2023 PTN Annual Review is Now Available

young family happily bonding together on the sofa at home

2023 was another busy and exciting year for the Pediatric Trials Network (PTN). This year, the Network upheld its commitment to improving pediatric care by changing labels, performing research, connecting with partners, and sharing science. The PTN would like to thank its participants, members, and partners for their continued support in making a difference for children and families worldwide!

This year, the PTN contributed data to two U.S. Food and Drug Administration (FDA) medication label changes. FDA label changes help health care providers prescribe the safest, most effective dosages of medicines to children. These label changes make 19, in total, that the PTN has informed to date. Three PTN studies reached milestones in 2023. Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose Intravenous Methadone in Healthy Adult Volunteers (MTH02) enrolled its first participants; CUDDLE added seven medications to the list of those being studied; and the Safety of Sildenafil in Premature Infants study opened its third and final cohort. Including these, the PTN supported six ongoing studies in 2023, and one new study is expected to begin enrolling in 2024.

Throughout 2023, the PTN connected with its partners at the Pediatric Academic Societies Annual Meeting and the International Children’s Advisory Network (iCAN) Summit. Events at these meetings included a debate between PTN investigators and informational sessions on the work of PTN and iCAN.

Since last year’s report, the PTN has released four new publications and three new results-at-a-glance summaries. Additionally, the PTN started sharing its methods for analyzing various biological samples with the scientific community.

Access the 2023 PTN Annual Review.

PTN Research Informs Fluconazole Label Change

Data from multiple Pediatric Trials Network (PTN) studies contributed to a recent U.S. Food and Drug Administration (FDA) label change for fluconazole. The data that informed the label update, which is extensive, came from the following studies:

  1. Fluconazole Prophylaxis for the Prevention of Candidiasis in Infants < 750 Grams Birth Weight
  2. Pharmacokinetics of a Fluconazole Loading Dose in Infants and Toddlers
  3. Safety and Pharmacokinetics of Fluconazole in Children Supported by Extracorporeal Membrane Oxygenation (ECMO)
  4. A Multicenter, Open Label Pharmacokinetics Study of Fluconazole in Infants

Previous labels for the medicine fluconazole contained almost no information related to dosages for infants, even though it is commonly used to treat Candida (yeast) infections, particularly in the neonatal intensive care unit (NICU) and pediatric intensive care unit (PICU). These infections are often fatal in infants and cause long-lasting health problems for those that survive, so determining how to best use fluconazole for this population was vital.

The new label contains information submitted by PTN on pharmacokinetics and dosing suggestions, as well as safety and efficacy of fluconazole for both treatment and prevention of Candida infections in full-term and premature infants.

Important additions to the fluconazole label include:

  • Pharmacokinetic data on fluconazole in infants
  • Suggestion of use of a loading dose for children
  • Information on dosing for pediatric patients being supported with extracorporeal membrane oxygenation (ECMO)
  • Information on the use of fluconazole for prevention of Candida infection in infants

This is the 20th FDA label change informed by PTN research. This achievement represents the culmination of >15 years of work on fluconazole from faculty and staff at PTN, in addition to collaborating sites and thought leaders across the U.S. The PTN is grateful to the children and families who participated in the important studies that led to this label change.

Dumela Botswana! PTN Research on Breastfeeding Looks at Antiretroviral Medications

The Pediatric Trials Network (PTN) said “Dumela” (hello in Setswana) to Botswana as it activated a Botswana-based site in January. The site has already enrolled several participants in the Pharmacokinetic and Safety of Antiretroviral and Related Drugs in Lactating Women and Breastmilk Fed Infants (BMS02) study. This study will help answer important questions about breastfeeding for women living with HIV/AIDS around the world.

Botswana, like many other countries in Africa, was hit hard by the HIV/AIDs pandemic more than a decade ago. However, with its government’s leadership and commitment to providing free antiretroviral medications, the once devastating disease has become a chronic condition for many. Today, over 20% of the adult population lives with HIV and 82% of those people take antiretroviral medications every day. But many women taking these medications who are also breastfeeding their infants have unanswered questions about safety. While studies indicate that the transmission of HIV from mother to child is reduced if the mother is on antiretroviral medications, there are not many studies that describe the extent of antiretroviral drug transfer into breastmilk. Because of the prevalence of HIV in Botswana and its government’s commitment to treating the disease, many women are likely to be interested in helping to find answers to these important questions. The BMS02 study will specifically study the following drugs:

  • Dolutegravir
  • Emtricitabine
  • Tenofovir disoproxil fumarate
  • Lamivudine

A better understanding of the safety of common antiretroviral medications in breastfeeding infants will provide data to help clinical professionals everywhere to advise breastfeeding mothers who live with HIV/AIDs. Confirmed safety might promote breastfeeding and benefit both mothers and their children.

This partnership will build on collaborations that Duke University Associate Professor of Pediatrics and Global Health, Matthew Kelly, MD, MPH has already established with Botswana.
“We are so excited to partner with PTN on this important study that has implications both nationally and internationally for women and their infants,” said Dr. Kelly. “This is an important question for women living with HIV everywhere.”

“We are happy to build on UPenn’s existing collaboration,” said Angelique Boutzoukas, Principal Investigator for the Project. “Expanding PTN research into low- and middle-income countries, such as Botswana, means that PTN can expand its mission to impact even more children’s lives through better evidence for medications.”

PTN Enrolls Participants in Methadone Study for Adults

Nurse puts her hand on an adult patient's shoulder

The Pediatric Trials Network (PTN) has enrolled the first participants in a study titled Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose Intravenous Methadone in Healthy Adult Volunteers (MTH02).

This study will evaluate how healthy adults process methadone administered through IV. It is essential for determining the optimal dose of methadone and to understand variations in drug disposition. Methadone is already approved by the U.S. Food and Drug Administration (FDA) for pain management in adults. Results from MTH02 will help update information on dosing methadone for adults, and they will lay the foundation for studies to label methadone for treating acute pain for children.

Dr. Kanecia Zimmerman
Kanecia Zimmerman, MD, PhD, MPH

“Children can experience pain due to various reasons, such as illness, injury, medical procedures, or chronic conditions. It is crucial to manage their pain effectively to improve their comfort, promote healing, and enhance their overall well-being,” said Dr. Kanecia Zimmerman, the principal investigator of the study. “The Adult Methadone Study is being conducted to understand how drugs, such as methadone, can help. Studying methadone in the adult population first brings us one step closer to answering the questions surrounding the safety and optimal dosing of methadone in children.”

To learn more about Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose Intravenous Methadone in Healthy Adult Volunteers visit ClinicalTrials.gov.

Investigator Spotlight: Dr. Susan Rahman

Q: Could you tell us about yourself (background, areas of interest, expertise, etc.)?

A: I’ve been a pediatric researcher and innovator for nearly 30 years overseeing basic, clinical, and translational research programs. I’ve been funded by an array of sponsors (e.g. the National Institutes of Health, World Health Organization, Centers for Diseases Control and Prevention, National Endowment for the Arts) and have had the opportunity to conduct research in over a dozen countries across 4 continents. But no matter the location or sponsor, the focus of my research has always centered on improving the health of underserved and underrepresented populations.

Q:What PTN studies are you currently involved with? What are you hoping to learn from the study/studies?

A: I’m currently providing oversight for two studies as part of the PTN Diversity Metrics group. The first is a project examining the changes that get introduced to study protocols over their lifetime in hopes of understanding the extent to which patient burden is added or alleviated by sponsors and regulators. The second study is similarly themed and explores the extent to which investigators and participant families share perceptions of the burden carried by a study and its related protocol elements.

Q: Can you recall an especially impactful encounter with a participant and/or family of a participant?

A: As a clinician caring for the patients I engage in research, there are more poignant interactions than I can count. However, our recent implementation research has been particularly rewarding. We are developing solutions that empower parents and community health workers to improve the health and wellbeing of children in their homes and villages. Not only have we observed a measurable impact on child health, but we’ve heard directly from families about how meaningful these tools have been to them. It’s easy to forget that almost half of the world’s population doesn’t have access to basic health services so developing practical and sustainable solutions to address these gaps is incredibly satisfying.

Q: Why is the work of PTN important to you?

A: Any effort made to ensure the judicious use of medications in children should be lauded. However, what sets the PTN apart is their focus on medicines that might otherwise fail to receive the attention of researchers and their commitment to ensuring that the information garnered finds its way into the product label. It’s not just about conducting research and sending the results into the ether, but about working hard with regulatory colleagues to guarantee meaningful dissemination and application of the findings.

Q: What goals do you hope to achieve through your PTN-related work?

A: Through my current work with the PTN, I hope to remind pediatric researchers that the single most important partners we have are the patients, families, and communities we serve. They are an asset that we cannot undervalue, and we should strive to be purposeful in protecting this asset as we design and execute pediatric clinical trials.

PTN’S CUDDLE Study Will Assess Additional Drugs

Mother and baby

Pediatric Trials Network (PTN)’s BMS study (NICHD-2017-BMS01) of Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants (CUDDLE), has added new drugs to the list of drugs being studied; marking a substantial milestone in determining the safety of drugs passed through breastmilk.

The study will assess the following additional drugs to determine safety for both mothers and their breastfed infants.

  • Amoxicillin
  • Bupropion
  • Buprenorphine
  • Duloxetine
  • Hydrocodone
  • Levetiracetam
  • Paroxetine

It is common for new mothers to have symptoms or medical conditions that must be treated with drugs. With this study, PTN will find doses of commonly used drugs that are safe for both mothers and their breastfed infants.

“Many moms often are faced with the decision to either stop breastfeeding or discontinue their needed medications. We want to remove the mystery from this decision and help allow moms to breastfeed without additional burden,” said Kanecia Zimmerman, MD, CUDDLE PI, associate professor of pediatrics at Duke University School of Medicine.

See the NIH LactMed database for more information on the levels of various substances in breastmilk and infant blood, and possible adverse effects.

 

PTN Research Informs Levetiracetam Label Change

Hands hold a paper cut out of a head with brain waves on a purple background.

A pharmacokinetic (PK) study by the Pediatric Trials Network (PTN) has contributed to a recent label change for levetiracetam, an anti-epileptic drug. The U.S. Food and Drug Administration (FDA) updated the dosage information for levetiracetam based on the PTN studies Pharmacokinetics of Anti-epileptic Drugs in Obese Children (AED01) and Pharmacokinetics of Understudied Drugs Administered to Children per Standard of Care (POP01).

These studies were needed to evaluate the potential impact of obesity on the PK of levetiracetam. Incorrect dosing for children with obesity could increase the risk for drug toxicity or therapeutic failure.  The PK analysis included 164 obese and non-obese participants between the ages of 2 and 18 years. Results from the study provided data on how children with obesity processed levetiracetam differently from children without obesity. The updated levetiracetam label includes this valuable information for clinicians to keep in mind as they prescribe the drug for individual patients.

This is the 19th FDA label change informed by PTN research, a huge milestone toward the PTN’s goals. Thanks to the collaborative efforts of the studies, medical providers now have important information when using levetiracetam to treat seizures in pediatric patients with obesity.

 

PTN Team Presents at Annual iCAN Summit

PTN sponsor table at iCAN Summit

Members of the Pediatric Trials Network (PTN) team recently had the opportunity to attend, participate, and present at the 2023 International Children’s Advisory Network (iCAN) Summit in La Jolla, California.

Global Trials Associate Director, Phyllis Kennel, and Research Communications and Engagement Specialist, Meagan Daly, presented to a group of young people and industry representatives. The presentation familiarized the group with the important work of DCRI Pediatrics and PTN. The presentation also provided updates on the ways in which iCAN participation has helped inform the work of PTN.

One of the most recent collaborations between iCAN and PTN has centered around the development of a pediatric anthology. This body of work includes contributions from pediatric patients and are reflections on their experience with pediatric clinical care. The ultimate goal is to produce a hard copy of this content that will be made available as an engagement tool for DCRI pediatric trial participants.

iCAN is a worldwide consortium of children’s advisory groups, known as Kids Impacting Disease Through Science (KIDS) and Young Persons Advisory Groups (YPAGS). These dedicated youth member groups work in unison around the world to provide a voice for children and families in medicine, research, and innovation.

PTN served as a sponsor of the 2023 Summit along with Jumo Health, Pfizer, Bio Cryst, Fortera, Lilly, and others. Presence at the Summit afforded a variety of networking opportunities and fruitful discussions with industry sponsors to ensure we all working together to advance clinical research and care for pediatric populations.

PTN looks forward to a continued partnership with iCAN and all the opportunities it provides in helping advancing the care of our youngest patients.

PTN Sildenafil Study Opens Final Cohort

Image of baby hands

The Pediatric Trials Network (PTN) has opened the third cohort, or group of study participants, in the second phase of the Safety of Sildenafil in Premature Infants study. This is a major study milestone as it will help determine the safety of a higher dose of sildenafil in premature infants. Each cohort has received a different dose of sildenafil. The third, and final, cohort will receive the highest dose of 1 mg/kg.

The study aims to assess the safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia (BPD) and determine preliminary effectiveness and pharmacokinetics (how a drug travels through the body). BPD is a common chronic lung disease that can affect premature newborns, often leading to life-long medical problems, prolonged hospitalization, and even death. Approximately 17,500 U.S. infants develop BPD each year.

Sildenafil, which is approved for the treatment of pulmonary hypertension in adults, may help improve lung development and is increasingly being used off-label in premature infants developing BPD. However, there is still very little high-quality efficacy and safety data of sildenafil in premature infants.

Headshot of Jason Lang“BPD is a serious, and potentially life-long lung problem for premature infants. It is critical that we better understand how drugs, such as sildenafil, can help. Opening our third and final cohort is especially exciting because it gets us one step closer to answering the questions around safety and optimal dosing of sildenafil in infants,” said Dr. Jason Lang, the study’s Principal Investigator.

To learn more about Safety of Sildenafil in Premature Infants visit ClinicalTrials.gov or the PTN sildenafil study page.

PTN Now Provides Methods for Analyzing Drug Concentration

Gloved hand picks up a test tube with plasma.

Many PTN studies measure the concentration of certain drugs in children’s bodies. The PTN collaborates with several laboratories to develop and validate methods for analyzing biological samples. The PTN is now sharing these methods with the research community.

The PTN Methods page contains a list of drugs studied by the PTN along with the type of sample (plasma, dried blood spot, urine, cerebrospinal fluid, and breastmilk) used to evaluate drug concentration. There are over 200 methods available for 90 drugs. The process to gain access to these methods is simple; interested individuals should complete the Methods Sharing request form and email it to PTN-Program-Manager@dm.duke.edu.

The development and sharing of these methods are made possible through PTN’s large network of pediatric clinical research sites across 45 U.S. states and four additional countries. Together, they have studied 20 therapeutic areas and have enrolled over 12,500 participants.