Mercy babyTAPE approved for marketing

The U.S. Food and Drug Administration (FDA) has approved marketing of Mercy babyTAPE. Developed by PTN’s Dr. Susan Abdel-Rahman of Children’s Mercy Hospital, the Mercy babyTAPE device is intended for use by health care professionals to estimate the body weight of infants from birth to 90 days of age.

“Weight is the foremost marker of health and health outcomes in infants. A weighing scale remains the universal gold standard for obtaining weight in children and is highlighted by the World Health Organization as one of four essential pieces of equipment needed when caring for newborns. However, the vast majority of healthcare providers in remote, resource-constrained settings simply do not have access to functional, calibrated scales with the precision necessary to accurately determine weight,” Dr. Abdel-Rahman said.

Many critically ill newborns in the U.S. suffer similar challenges when it comes to weight assessment. For infants receiving care in a neonatal intensive care unit, it can be nearly impossible to remove or account for the weight of life-sustaining medical equipment, prior to obtaining a scale-based weight. The relative error introduced by such equipment can significantly affect the safety profile of the medicines these infants receive. As a result, dosing errors are more likely to occur.

The approved marketing of Mercy babyTAPE is a substantial accomplishment in PTN’s quest to improve healthcare for children by determining optimal dosing of commonly used medications.

New project supports inclusion of children with Down syndrome in clinical trials

Portrait of beautiful young girl on the playground

The Pediatric Trials Network (PTN) has received an award to contribute to the National Institutes of Health’s (NIH) INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) project. The INCLUDE directive calls for a trans-NIH research initiative to address critical health and quality-of-life needs for individuals with Down syndrome across the lifespan.

One of the three primary components of the INCLUDE initiative is to support clinical trials on conditions and diseases that affect people with Down syndrome, both to accelerate the development of new therapies for individuals with Down syndrome and to include them in ongoing clinical trials.

PTN will work to characterize the pharmacokinetics (PK)A, pharmacodynamics (PD)B and pharmacogenomics (PGx)C of understudied off-patent drugsD administered to children and young adults with Down syndrome. By studying individuals who are receiving these drugs as part of routine care provided by their physicians, researchers will be able to determine if the doses of medications given to individuals with Down syndrome are appropriate and safe.

Additionally, investigators will work to develop a training program for clinical researchers, both within the PTN and with external Down syndrome experts, to provide insight and guidance in trial design, recruitment, and engagement specifically in this population.

Down syndrome is a condition in which a person is born with an extra copy of chromosome 21. The condition is associated with intellectual disability, a characteristic facial appearance, and weak muscle tone, particularly in infancy. Children with this condition may have a variety of associated co-morbidities. For example, about half of all affected children are born with a heart defect, and there are high rates of hearing loss, thyroid disease, autoimmune conditions, sleep apnea, and certain types of cancers in individuals with Down syndrome.

The National Institute of Child Health and Human Development (NICHD) supports this work through the Best Pharmaceuticals for Children Act (BPCA). Dr. Daniel Benjamin, Principal Investigator and Chair of PTN, will partner with Dr. Mara Becker of the Duke Department of Pediatrics as the INCLUDE Principal Investigators. For more information on the NIH’s efforts to support children with Down syndrome and their families, visit DSConnect.

Reading Guide

A Pharmacokinetics (PK): How a drug travels through the body

B Pharmacodynamics (PD): The effects of a drug

C Pharmacogenomics (PGx): How genes affect a person’s response to a drug

DOff-patent drug: Also referred to as a “generic drug,” it is not protected by patent but contains the same chemical substance as a drug that was originally protected by chemical patents

 

First participant enrolled in digoxin study

The PTN digoxin study achieved a major study milestone by enrolling its first participant. The study team aims to enroll up to 48 infants to determine the pharmacokinetics (how a drug travels through the body) and safety of digoxin prescribed to infants with single ventricle congenital heart disease (CHD).

While digoxin has been approved by the U.S. Food and Drug Administration for the treatment of heart failure in children and adults, more information is needed, particularly in children with single ventricle CHD.

Each year 40,000 infants born in the U.S. are diagnosed with CHD. Single ventricle CHD is the most serious and complex form of the disease. Currently, there are no drugs proven to reduce death during this period.

According to study Principal Investigator, Dr. Christoph Hornik of the Duke Department of Pediatrics, “Despite significant efforts by a number of different providers that treat infants with CHD, the mortality rate remains quite high and there are no drugs that have been shown to decrease mortality.”

This study will try to answer questions about the side effects of digoxin and learn more about how it is processed in the bodies of children with single ventricle CHD.

“Digoxin is an old drug, but there is some evidence to suggest it may be helpful, so studying it in this population is essential,” said Hornik.

To learn more about the digoxin study visit ClinicalTrials.gov.

Sildenafil safety study achieves major milestone

The Pediatric Trials Network (PTN) recently enrolled the fortieth infant in the Safety of Sildenafil in Premature Infants study. This is a major study milestone, as it rounds out the first cohort (or group of study participants).

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). The study aims to enroll a total of up to 120 participants.

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 with BPD. However, the efficacy and safety of sildenafil in premature infants at risk for BPD is currently unknown.

“Our hope is that this study benefits premature infants and their families by providing more information on the safest and most effective dose of sildenafil to treat this life-threatening condition,” said Dr. Matthew Laughon, principal investigator and neonatologist at the University of North Carolina Hospitals in Chapel Hill, N.C.

To learn more about Safety of Sildenafil in Premature Infants visit ClinicalTrials.gov.

iCAN 2019 summit helps inform pediatric clinical research

The annual International Children’s Advisory Network (iCAN) Summit took place June 24-28 in Kansas City, Mo. Representatives from the Pediatric Trials Network (PTN) were in attendance, along with global representatives from pharmaceutical and clinical research groups.

The mission of iCAN is to empower pediatric patients worldwide by providing children and families a voice in health, research, medicine, and innovation. “One of iCAN’s goals is to educate the world—especially our youth—about the importance of not only participating in clinical trials, but also of being actively involved in the process of designing pediatric clinical trials,” said Leanne West, president of iCAN and chief engineer of pediatric technologies at the Georgia Institute of Technology in Atlanta, Ga.

The summit included a number of sessions that explored pediatric clinical research and patient engagement from unique viewpoints. PTN Program Manager Phyllis Kennel and PTN Project Leader Cheryl Alderman both attended the summit. “Having the opportunity to watch youth and their parents learn and grow in their knowledge of clinical research and how they can impact outcomes was an amazing experience,” Kennel said. “The passion that they have to improve clinical care for children is inspiring and I believe our future is in great hands.”

Three Different Perspectives of a Case Study: Patient, Parent, and Provider

Hannah Nilsson was diagnosed with Burkitt lymphoma, a rare and highly aggressive disease, when she was only 13 years old. After spending nearly 300 days in the hospital, and experiencing a reoccurrence after nine months, Hannah went on to graduate high school and college and is now a mother, wife, and full-time professional.

After Hannah’s experience, her mother, DeeJo Miller, devoted her life to helping families who enter the hospital system with their children. “I was hired by Children’s Mercy Kansas City as a ‘parent on staff’ in 2008 to collaborate with staff by serving as a voice of the families.”

Dr. Karen Lewing, director of medical informatics for hematology/oncology at Children’s Mercy, was also part of the session and shared her impression of the journey Hannah and DeeJo experienced.

This session shed light on the unique experiences patients, parents, and providers have while addressing a vital health need and how all parties can collaborate to ensure patients receive the best treatment.

The Role of the Institutional Review Board (IRB)

This session explored the purpose of an IRB and provided young attendees with an opportunity to review a study protocol to determine if the materials met the criteria for IRB approval. The activity gave session attendees an intimate look at and hands-on experience with the IRB process and how it ensures the rights and welfare of human subjects are protected. 

Patient Engagement: The Power of Patients in Healthcare

Kelly Ranallo, founder and president of the Turner Syndrome Global Alliance (TSGA), became a parent advocate after her daughter was diagnosed with Turner Syndrome, a chromosomal condition that affects development in women and girls. As part of her commitment to helping other parents with children diagnosed with rare diseases, Kelly built RareKC, a non-profit organization established to accelerate the diagnosis, care and treatment of rare conditions through patient-driven collaboration and innovation.

This session highlighted the support available for parents who have children with rare diseases. It also incorporated a tour of Mercy Children’s centers for genomics and innovation, which work to implement groundbreaking ideas in the rare disease field.

iCAN and PTN Partnership

The Pediatric Trials Network (PTN) has established a partnership with iCAN in an effort to engage participants and their families in research conducted by PTN. As part of the partnership, iCAN will review the design of PTN trials as well as patient consent and recruitment materials to ensure they actively involve participants and their families and take their needs and concerns into consideration.

“Giving children and families an active role in the design of clinical studies that affect them is critical, not only for conducting the highest quality and most meaningful research, but also for making the experience as positive as possible for everyone involved,” said Dr. Danny Benjamin, principal investigator for the PTN. “If we can help make the experience better for children, we’ve achieved our goal.”

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Investigator shares successes, lessons learned from PTN, IDeA States partnership

During a PTN-hosted symposium at the Pediatric Academic Societies (PAS) Annual Meeting on Sunday, April 28, Dr. Janice Sullivan of the University of Louisville School of Medicine discussed the successes and lessons learned from the IDeA States Pediatric Clinical Trials Network’s (ISPCTN) participation in the PTN POPS Study.

The ISPCTN is one component of ECHO (Environmental Influences on Child Health Outcomes), an NIH-funded initiative launched in 2016 to study the effects of early environmental exposures on child health and development. The ISPCTN’s 17 sites are tasked with conducting clinical trials with a focus on rural and underserved areas.

“[These sites] do not typically get a lot of federal dollars to support research, so there are a lot of unique needs in these areas,” Dr. Sullivan said. “It was challenging in those first months trying to figure out how to organize ourselves and move things forward.”

The PTN offered the opportunity for ISPCTN sites to participate in POPS (Pharmacokinetics of Understudied Drugs Administered to Children Per Standard of Care), a study designed to determine the safest and most effective doses of a variety of understudied drugs that are regularly prescribed to children.

The ISPCTN agreed to join the study in June 2017. It was a quick way to get involved in a low-risk clinical trial, Dr. Sullivan said, because patients were already receiving the drugs and blood samples were being collected as part of regular care. In addition, POPS was in line with the goals of ISPCTN and provided an opportunity for capacity building and mentorship.

“The PTN did an incredible job trying to prepare these sites,” Dr. Sullivan said. They provided each site with a study overview and detailed agenda for their qualification visits, toured the facilities and met staff at each site, and came prepared with a list of additional items to discuss.

Despite this preparation, there were still challenges. When the ISPCTN sites joined POPS, many of them had no experience negotiating contracts. Others required oversight of a tribal IRB, which required working through these specific needs. Many had to develop new policies for specimen storage, equipment maintenance, temperature monitoring, and dealing with different systems for electronic medical records.

After working to address these issues, Dr. Sullivan said, the sites got up to speed incredibly quickly. Fourteen sites have been activated to date and have enrolled a total of 139 patients. In addition, sites had to work internally to determine how to query their electronic medical record to identify potential subjects. Within a few months some sites were able to reduce their data query time from several hours to about 20 minutes.

Dr. Sullivan pointed to five common themes that determined success: getting sites enrolling, engaging new sites and investigators, building capacity, improving the network’s interaction with the IRB and regulatory agencies, and gaining buy-in and engagement from patients and the community.

Everyone has benefited from the partnership, she added, especially the children. The PTN has reached out to several ISPCTN sites to invite them to get involved in additional studies. “This will really help us be more sustainable and help us collaborate,” she said. “Sharing of ideas has helped everyone win.”

Investigators explore PTN’s impact on clinical practice at PAS

During a PTN-hosted symposium at the annual Pediatric Academic Societies (PAS) Meeting on Sunday, April 28, Dr. Kelly Wade of the Children’s Hospital of Philadelphia and Dr. Matthew Laughon of the University of North Carolina at Chapel Hill shared how PTN’s work is informing on the doses of medications commonly given to infants in the neonatal intensive care unit (NICU).

While improved survival of the smallest, most premature babies is a victory for health care, Dr. Wade said, it also presents a challenge: ensuring a safe passage through a sometimes months-long stay in the NICU. This stay often involves a number of medications that are prescribed “off-label,” or without specific safety and dosing information for this particular – and very vulnerable – population. The NICU, she said, presents a unique opportunity to study these medications in the youngest patients to learn how to dose them appropriately and, consequently, improve their outcomes.

According to a PTN publication, 65 percent of the top 100 most commonly prescribed medications are not adequately studied or labeled for use in the NICU. The PTN is making it a priority to study a number of these drugs, especially “top-10” drugs such as ampicillin, furosemide, and caffeine. These three medications alone, Dr. Laughon said, represent 80 percent of off-label use in the NICU.

“The PTN is really going for these high-effect, high-impact type studies,” he said.

Since this population is so vulnerable, however, there are a number of challenges to enrolling babies in these studies. Dr. Laughon listed a number of measures that the PTN has put in place to make sure the studies are minimally burdensome on these children and their families.

“The blood sampling is aligned with standard of care to prevent extra needle sticks, smaller blood volumes are taken, and sometimes we’re able to measure two or more drugs in a single sample,” he said.

Drs. Wade and Laughon pointed out the wide variation in dosing of ampicillin, the most commonly used drug in the NICU. To ensure infants were getting the safest and most effective dose of this drug, PTN did a study of 73 babies that used standard of care dosing. The results of the study indicated that the most common dose used in clinical care is probably too high, and that high doses of ampicillin may increase the risk of seizures.

Dr. Laughon added that there are currently no FDA-indicated therapies for the prevention or treatment of bronchopulmonary dysplasia (BPD), a chronic lung disease that affects mostly preterm and term infants. The PTN is conducting a randomized study that has enrolled 80 participants so far to determine the appropriate dose of furosemide, the top diuretic used to treat BPD.

In addition to studying these medications, PTN work has led to recent label changes for meropenem for intra-abdominal infections and acyclovir for herpes simplex infection. Data are also currently at the FDA to support label changes for piperacillin-tazobactam and fluconazole, and are currently being collected for anti-staph antibiotics, furosemide, sildenafil, and timolol for the treatment of infantile hemangiomas (often called strawberry birthmarks).

“We still have a lot of work to do to understand what’s the best dose to provide the optimal response,” Dr. Wade said.

PTN LAPS Trial enrolls more than 100 patients

The PTN Long-term Antipsychotic Pediatric Safety (LAPS) Trial, which aims to assess the long-term health risks of risperidone and aripiprazole in children, has now enrolled more than 100 children. Risperidone and aripiprazole have been shown to be effective for the treatment of conditions such as schizophrenia and bipolar disorder in adults, but little is known about the long-term health risks and quality-of-life benefits for their use in children.

While several antipsychotics are FDA-approved in children, it is common for these drugs to be prescribed without FDA approval for conditions such as attention-deficit disorder, obsessive-compulsive disorder, and major depression.

The ultimate goal of the study is to provide long-term safety data to the FDA to update the risperidone and aripiprazole labels to include correct safety and dosing information. This information will allow doctors to provide the safest, most effective dose to children who require treatment with antipsychotics.

The enrollment of more than 100 children helps achieve nearly 30 percent of the overall enrollment goal of the LAPS Trial and is a key accomplishment for the two-year observational study.

PTN Evaluates Systemic Exposure of Timolol as Treatment for Infantile Hemangiomas

The Pediatric Trials Network (PTN) recently published research in the Journal of the American Academy of Dermatology (JAAD) that explores whether topicaltimolol used on infants is absorbed through the skin and can be detected in the blood. The newly published research shares findings from a study led by Drs. Beth Ann Drolet and Kristen Holland of the Medical College of Wisconsin in Milwaukee. In this study, 76 children less than two years of age receiving timolol, as prescribed by their doctor, were monitored for a 90-day period and blood samples were collected.

Timolol is a beta blockerB that has increasingly been used for the treatment of Infantile Hemangiomas (IH), also commonly called “strawberry” birthmarks, on infants’ skin. However, little is known regarding the safety of topical timolol’s use.

In the PTN study, 75 children received a 0.5% concentration of timolol and one child received 0.25%. While it was predicted that young infants would have higher concentrations of timolol in their blood, the study found that older infants and those with thicker hemangiomas had the highest concentrations. There were no reports of serious unexpected adverse events during the 90-day study period.

An additional Phase IItrial will aid in determining the best and most effective dose of timolol in infants. However, the published research indicates that two drops of 0.5% timolol per day should not be exceeded in the treatment of small, thin hemangiomas. For the treatment of thicker hemangiomas, oral medicationD is recommended.

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

 


Terms Guide

ATopical – Medication applied to body surfaces, such as the skin

BBeta Blocker – Medication that reduces blood pressure

CPhase II – A trial that explores the effectiveness of a medication that can last several months to years, and involve several hundred patients  

DOral Medication – Medication taken by mouth

FDA approves Zovirax (acyclovir) labeling supplement

Research conducted by the Pediatric Trials Network (PTN) has led the U.S. Food and Drug Administration (FDA) to update the prescribing information, or drug label, of acyclovir to include dosing for infants with Neonatal Herpes Simplex Virus (HSV) based upon the infants post-menstrual age. Acyclovir (brand name Zovirax) is an antiviral drug used in the pediatric population to treat HSV, a highly contagious virus that can be very serious for babies.

Because an infant’s immune system is not fully developed to fight off the virus, the disease can result in death or mental disabilities. While appropriate dosing of acyclovir was known for adults and children, acyclovir had not been adequately studied in full-term or preterm infants.

In the two associated PTN studies, 32 infants were enrolled. The first study was conducted at a single medical center in preterm and term infants with suspected HSV infection. The second study involved multiple medical centers and enrolled only preterm infants with suspected HSV infection.

Based upon the pharmacokinetic (how a drug travels through the body) results, the FDA updated the label to include dosing in infants based on their post-menstrual age (PMA), or the time that had elapsed since the mother’s last menstrual cycle. PMA is especially useful in preterm infants because it characterizes the baby’s expected developmental age.