FDA changes lithium label to reflect appropriate dosing for children

The U.S. Food and Drug Administration (FDA) recently updated the label for the drug lithium to include appropriate dosing for children. The change was made after a trial supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) showed that lithium was safe and effective for children with bipolar disorder. Prior to this change, lithium had no safety or dosing information for anyone under age 18.

Researchers enrolled 81 children ages 7 to 17, who were divided into two groups. Fifty-three received lithium for a period of 8 weeks, and 28 received a placebo. Based on a questionnaire, researchers found that children receiving lithium experienced improved symptoms over those in the placebo group. In addition, children taking lithium did not experience significant metabolic side effects such as weight gain, as compared to other medications for bipolar disorder.

The Best Pharmaceuticals for Children Act (BPCA), which became law in 2002, funds research on medications for infants and children. The PTN was created by NICHD to make these pediatric trials more efficient. Read more on the NICHD website.

PTN Spotlight: Paula Delmore, Wesley Medical Center

Paula Delmore, left, with Dr. Barry Bloom, Wesley Medical Center Medical Director

Paula Delmore has actively participated in the support of clinical research for the past 30 years. Although the majority of her expertise is in the role of site study coordinator, she has served in the roles of multi-site coordinator, sub-investigator, and principal investigator. Her main strengths lie in her attention to detail and solid understanding of clinical trial execution in the neonatal area. Her team routinely performs as a highest enroller, which speaks to her exemplary coordination and good communication with providers, nursing staff, and families. We sat down with Paula to learn more about her work and involvement with the Pediatrics Trial Network.

Q: How long have you worked at Wesley Medical Center and what are your primary responsibilities?

A: I have been at Wesley Medical Center for 40 years and currently work in an administrative role. I supervise nurse practitioners, physician assistants, and support personnel with the Neonatal Intensive Care Unit (NICU).

Q: How does your role as a site coordinator with PTN overlap with your responsibilities as part of the Wesley Medical Center administrative staff?

A: I’ve been working with our Medical Director, Dr. Barry Bloom, for 35 years as a research coordinator. Over time, my role has advanced from being a research assistant to coordinating studies, and at times, being the principal investigator. I have been the principal investigator for a couple of PTN studies, most recently the PTN Baby TAPE study.

Q: How long has Wesley Medical Center been part of PTN?

A: From the very beginning! We were one of the first centers in the Rapid Start Network. We participated in the Fluconazole Safety study and all the early Pharmacokinetic (PK) Antibiotic studies.

Q: What have you found to be the most rewarding aspect of PTN?

A: PTN covers the gamut of pediatrics, but what I find most rewarding and exciting is that they continue to explore new therapies for neonates, and also validate standard practice where there is no prior evidence.

Q: Is there an experience you’ve had with PTN that has been particularly impactful?

A: Right now we are participating in the Sildenafil II study. As part of that study, it’s really great to work with families and offer them something that could potentially help their baby. Even though everything is an unknown, and we aren’t sure it’s going to help, it’s nice to offer parents the chance that our research and efforts will benefit their child. In general, giving families another option for excellence in care is what I find to be the most impactful.

Q: Why would you recommend other investigators become a part of PTN?

A: The responsiveness of the lead investigators is phenomenal. When questions arise, they are ready and available to answer and are very timely. This allows for the seamless continuation of patient enrollment and helps in meeting the randomization timelines. The PTN studies are some of the most organized and efficient I’ve been a part of.

Database locked for SCAMP study

The Pediatric Trials Network (PTN) has locked the database for the Antibiotic Safety in Infants with Complicated Intra-abdominal Infections (SCAMP) study. The study, which enrolled its first patient in 2014, is designed to assess the safety, efficacy, and pharmacokinetics of three commonly prescribed antibiotic regimens for infants with intra-abdominal infections.

Complicated intra-abdominal infections (cIAIs) are common and often fatal in premature infants. The most common cIAI in neonates is necrotizing enterocolitis (NEC), a devastating disease that causes inflammation and can eventually destroy the wall of the bowel.

“In extremely low-birth-weight infants, the death rate for NEC can be as high as 50 percent,” said Dr. Michael Smith, investigator for the SCAMP study and associate professor of pediatrics at the Duke University School of Medicine. “Even survivors can suffer from lifelong complications such as short bowel-syndrome and poor neurodevelopmental outcomes.”

The most commonly used antibiotics in infants with cIAI include ampicillin, metronidazole, clindamycin, piperacillin-tazobactam, and gentamicin. However, since safety and efficacy data are lacking, these drugs are not labeled for use in infants with cIAI.

The PTN is filling this information gap with SCAMP, a partially randomized, multicenter, open-label study to determine the safety of these drug regimens in this specific and highly vulnerable population. Nearly 300 infants participated in the study at 58 sites in the U.S. and Canada. The infants were enrolled for 100 days, including 10 days of treatment and up to 90 days of follow-up assessments.

As a next step, the results of the SCAMP study will be submitted to the FDA for potential drug label changes.

PTN intern credits experience in STAR Program with passion for medical research

Daniel Gorham was a 17-year-old high school student when his mother, a data scientist at the Duke Clinical Research Institute, showed him an article about the Summer Training in Academic Research (STAR) Program.

Although he dismissed the idea at first, he began reading up on the program and became more intrigued. He applied in 2016, and it is a decision he doesn’t regret.

“I always knew I wanted to do something in the sciences, but I didn’t know which route I wanted to take,” he said. “Learning about the different career fields and meeting different doctors and professionals, I ended up learning more about myself.”

The annual STAR Program gives high school students, college students, and middle and high school teachers hands-on experience conducting an original research project. It also provides classroom training in epidemiology, global health, medical ethics, statistics, and writing.

Although Gorham was initially more interested in cancer research than pediatrics, the eight-week program changed his mind. He spent the summer researching bronchopulmonary dysplasia (BPD), a dangerous lung disease that affects approximately 17,500 premature infants in the U.S. every year, often leading to life-long medical problems and even death.

His research on how BPD impacts the lives of premature infants, along with lectures in neonatology and tours of the neonatal intensive care unit (NICU), quickly instilled a love of pediatrics. The fact that Gorham’s older brother had been born preterm made the research hit even closer to home.

“I had always heard these stories about how tiny and sick he was, and how his chances of life were so slim,” Gorham said. “After spending time on rounds and being around these babies and their families, I realized how important this work really is.”

After graduating from the program, Gorham kept in close contact with program director Dr. Danny Benjamin. When an opening became available for a summer intern at the Pediatric Trials Network (PTN), where Benjamin is principal investigator, Gorham jumped at the chance.

For the entire summer, he conducted research on blood plasma stability, or how certain drugs stay stable in the blood of infants and children. At the end of his internship, he presented his findings on 70 different drugs to an audience of doctors and other professionals at the DCRI.

Gorham is now returning to East Carolina University, where he will be a junior this year. After completing his degree, he plans to come back to Durham to take the next steps toward a career in pediatric research.

“When I say the STAR Program changed my life, it sounds cliché,” he said. “But without it, I would have ended up approaching a career that I didn’t have much passion for.”

He recommends the STAR Program to others, and has even encouraged three of his friends to apply.

“It takes you out of the mindset of a high school student and turns you into an adult,” Gorham said. “My outlook on science completely transformed from, ‘I need to get an A in this class’ to ‘This actually saves lives.’”

NICHD renews federal contract for Pediatric Trials Network

The Pediatric Trials Network (PTN) was recently awarded a contract by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to design and lead pediatric trials over the next eight years.

“Over the last eight years, we have been able to conduct 26 clinical trials in 13 different therapeutic areas enrolling over 8,000 children, which is more than triple the scope of work that was outlined in the initial NIH contract,” said Daniel Benjamin, Jr., MD, PhD, principal investigator and chair of the PTN.

Benjamin was the original awardee of the NIH contract in 2010. He and the PTN’s program manager, Gary Furda, helped secure the second award for an additional eight years. Additional DCRI faculty supporting the contract include Christoph Hornik, MD; Kanecia Zimmerman, MD; and Michael Cohen-Wolkowiez, MD, PhD.

“Danny and his primary supporters on the faculty side are outstanding in what they do and their passion for improving the health of children is unmeasured,” said Taylor Nguyen, a senior business development associate at Duke who was part of the grant-writing group. “The incredible results that the PTN team has produced over the course of the last eight years are largely due to their commitment and passion and how they go above and beyond in the work they do.”

“In the first eight years of the PTN, we were able to transform neonatal and obesity trials,” Benjamin said. “Over the next eight, we will have people rethink the way drug studies are done for breastfeeding women and mental health for children.”

Benjamin intends for the PTN to lead the way in revolutionizing the way clinical trials are conducted in children.

“We will continue designing larger trials and make these large trials more efficient,” he said. “With all the operational excellence at the DCRI, the junior and mid-career faculty, and our very determined staff at the PTN sites working together round the clock in various capacities and doing exceptional work for the network, no goal is big enough.”

Annual STAR Program for aspiring researchers now under way

The Summer Training in Academic Research (STAR) Program welcomed 21 participants at its kickoff event today. Now in its sixth year, the program provides hands-on research experience for undergraduate students, high school students, and high school teachers during the summer academic break.

“The STAR program is an excellent way for students to learn more about clinical research and how to effectively work in a collaborative environment,” said program leader Dr. Danny Benjamin, principal investigator for the PTN and faculty associate director of the Duke Clinical Research Institute (DCRI).

During the eight-week program, participants are placed in teams and matched with faculty mentors to work on original, hypothesis-driven projects. Participants also receive intensive instruction in developing scientific manuscripts, applied statistics, and data analysis. A goal of the program is to have every trainee qualify for co-authorship on a peer-reviewed manuscript related to their team’s project.

“I joined the STAR program because I want to be a neurosurgeon one day. Spending time with the STAR program mentors will help me determine if I’m on the right path to achieving my goals,” said Millbrook High school rising senior, Kennedy Hill.

The faculty of the STAR Program is actively involved in research sponsored by the National Institutes of Health (NIH). Combined, these faculty members have more than 200 publications with trainees as either first author or co-author.

In addition to the research project, program participants attend lectures on neonatology, antimicrobial therapy, pharmacoepidemiology, and medical ethics. Eligible students experience clinical medicine firsthand by shadowing a physician on hospital rounds.

Visit the STAR Program website for more information.

PTN creates data repository to aid in pediatric research

Dr. Christoph Hornik

Randomized clinical trials are considered the gold standard in clinical research. However, they often require a great deal of time and cost, and may not be feasible to conduct in vulnerable populations such as premature infants.

To overcome these difficulties, the Pediatric Trials Network (PTN) developed a repository of electronic health record (EHR) data gathered from nearly 265,000 pediatric patients to better guide research.

“This real-world data can be used to target drugs, conditions, and subpopulations for clinical studies that will maximize public health benefit and help identify areas for future study,” said Dr. Christoph Hornik of the Duke Department of Pediatrics, who led the development of the data repository.

The Best Pharmaceuticals for Children Act (BPCA) mandates the National Institutes of Health to prioritize areas where there is a critical need for information to guide medical treatments in children. With funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the PTN conducts studies designed to determine the dosing, safety, and efficacy of drugs that have been approved for adults but lack information for the pediatric population.

The repository, which includes data collected from 9 participating sites from 2013 to 2017, will aid in PTN’s mission by providing a multicenter data source to support its studies. It will facilitate both trial planning and the analysis of the uses and effects of a variety of medications in infants and children.

“Findings from this initiative will benefit children receiving care by not only shedding light on existing treatment practices, but also determining best practices for the future,” Hornik said.

The data collection, validation, and storage process was managed by Duke Health Technology Services and conducted in accordance with the Federal Information Security Management Act.

PTN to present at PAS 2018 Meeting in Toronto

The Pediatric Trials Network (PTN) will be presenting its research at the Pediatric Academic Societies (PAS) Meeting May 5-8 at the Metro Toronto Convention Centre in Toronto, Canada.

The annual PAS Meeting brings together thousands of researchers, academics, and clinical care providers united by a common mission: to improve the health and well-being of children worldwide. It is supported by the American Pediatric Society, the Society for Pediatric Research, the Academic Pediatric Association, and the American Academy of Pediatrics.

During the annual meeting, PTN investigators will share information on a variety of studies involving antibiotic safety, treatment of hospital-associated and ventilator-acquired bacterial pneumonia, infant weight estimation, personal protective equipment, and the development of a data repository to aid in pediatric research. See a detailed schedule of PTN-related presentations below or view the online program guide on the PAS website.

Saturday, May 5

  •  1:15 p.m. – Validation and Human Factors Evaluation of a New Device for Infant Weight Estimation – Dr. Susan Abdel-Rahman, Children’s Mercy Kansas City (Poster)
  •  1:15 p.m. – The Use of PPE during Pediatric Resuscitation: Which Tasks are Most Affected? The Results of a Survey during a Simulation Trial – Dr. Aaron Donoghue, Children’s Hospital of Philadelphia (Poster)

Sunday, May 6

  •  11 a.m. – The Impact of Personal Protective Equipment on Performing Critical Procedures for Pediatric Patients in the Pre-Hospital Setting – Dr. Maybelle Kou, Inova Fairfax Hospital (Platform)
  •  3:45 p.m. – Population Pharmacokinetics of Milrinone in Infants and Children – Dr. Christoph Hornik, Duke University (Platform)
  •  4:45 p.m. – Development of an Electronic Health Record Derived Multicenter Inpatient Pediatric Data Repository – Dr. Christoph Hornik, Duke University (Platform)
  •  5:45 p.m. – Hospital Associated and Ventilator Acquired Bacterial Pneumonias in Infants and Children – Dr. Jessica Ericson, Penn State Milton S. Hershey Medical Center (Poster)
  •  5:45 p.m. – Population Pharmacokinetics and Safety of Sildenafil in Premature Infants – Dr. Daniel Gonzalez, UNC Eshelman School of Pharmacy (Poster)

Monday, May 7

  • 2 p.m. – Antibiotic Safety and Efficacy in Infants with Complicated Intra-Abdominal Infections (cIAIs) – Dr. Michael Smith, Duke University (Platform)
  • 5:45 p.m. – Dosing-Safety Relationship for Acyclovir in the Treatment of Neonatal Herpes Simplex Virus Disease – Dr. Jessica Ericson, Penn State Milton S. Hershey Medical Center (Poster)
  • 5:45 p.m. – Impact of Personal Protective Equipment on Pediatric Cardiopulmonary Resuscitation Performance – Dr. Aaron Donoghue, Children’s Hospital of Philadelphia (Poster)
  • 5:45 p.m. – Weight Gain and Metabolic Syndrome in Children Exposed to Second-Generation Antipsychotic Medications – Dr. Angela Czaja, Children’s Hospital Colorado (Platform)

Tuesday, May 8

  • 7:30 a.m. – Correlating Pulmonary Hypertension by Echocardiogram with Mortality in Premature Infants – Dr. Rachel Torok, Duke University (Platform)

PTN welcomes first sites in Australia

The Pediatric Trials Network (PTN) welcomed its first two Australian sites in February. Sydney Children’s Hospitals Network and the Royal Children’s Hospital in Melbourne are now participating in PTN’s Pharmacokinetics of Understudied Drugs in Infants and Children (POPS) study.

The sites are currently involved in the Paediatric Trials Network Australia (PTNA), a counterpart of PTN that brings together pediatric researchers from across Australia who are committed to improving child health through the facilitation of pediatric clinical trials.

“These sites bring considerable experience in pediatric research and will make a significant contribution to PTN’s work,” said Dr. Danny Benjamin, principal investigator for the PTN. “In addition, their involvement will expand PTN’s global footprint, allowing us to gather data from a more diverse and widespread group of children and infants that can better inform our research.”

The POPS study is designed to assess the pharmacokinetics of a variety of commonly used drugs in children and infants that have limited safety and dosing information in the pediatric population. More than 70 drugs used to treat nearly 50 diseases and conditions have been studied so far.

Sydney Children’s Hospital, Randwick
Kids Research Institute, Westmead
Royal Children’s Hospital, Melbourne

Groundbreaking study to assess safety of drugs passed through breastmilk

The Pediatric Trials Network (PTN) is undertaking a groundbreaking study to assess the safety of commonly used off-patent medications when they are given to breastfeeding mothers. The study will track how different drugs are passed through breastmilk to determine dosing levels that are safe for both mom and baby.

Although the U.S. Food and Drug Administration (FDA) has implemented a guidance document on conducting lactation studies, off-patent drugs are not included in that rule. The PTN seeks to fill this knowledge gap.

Dr. Kevin Watt

“Although the benefits of breastfeeding are well-documented, we still don’t know enough about the effects of many prescription and over-the-counter off-patent drugs when they are passed to infants through their mother’s breastmilk,” said Dr. Kevin Watt, an assistant professor of pediatrics at Duke University who is leading the study. “As a rule, we discourage unnecessary drug use during lactation, but it’s quite common for new mothers to have symptoms or medical conditions that must be treated with drugs.”

“Many breastfeeding moms struggle with the decision to take medications because of the fear that these drugs will harm their children,” Watt said. “In the end, it often comes down to either stopping breastfeeding or discontinuing needed medications. We want to take the guesswork out of this decision and allow moms to breastfeed without worry.”

The study is expected to begin in April of 2018 and will enroll approximately 50 lactating women, along with their breastfed infants, for each drug studied. Initially 10 off-patent drugs will be studied, including medications used to treat bacterial infections, depression and anxiety, high blood pressure, diabetes, and chronic pain. Mothers will be enrolled in the study only if they are already taking one of the study drugs as part of their routine care.

Mothers who participate in the study will provide samples of breastmilk, their blood, their infants’ blood, or a combination to help researchers measure drug levels and determine the safest dose. Mothers and infants are expected to remain in the study until the infants reach 180 days of age.

The study, supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), will also explore the effects of maternal obesity on drug exposure and long-term outcomes of breastfed infants exposed to drugs in breastmilk.

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

 

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