PTN CUDDLE achieves study milestone

PTN’s study (NICHD-2017-BMS01) of Pharmacokinetics and Safety of Commonly Used Drugs in Lactating Women and Breastfed Infants (CUDDLE,) has completed study enrollment for nine off-patent drugs; marking a substantial milestone in determining the safety of drugs passed through breastmilk.

The study, which began in 2018, has enrolled approximately 50 lactating women, per drug, along with their breastfed infants. Enrolled mothers were already taking one of the following study drugs* as part of their routine care.

  • Azithromycin
  • Clindamycin
  • Labetalol
  • Metformin
  • Nifedipine
  • Ondansetron
  • Oxycodone
  • Sertraline
  • Tranexamic Acid

“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 the University of Utah Health and CUDDLE co-investigator.

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, and Co-PI for the PTN.

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

*The CUDDLE study will also assess the safety of Escitalopram, Ciprofloxacin, Doxycycline, Levofloxacin, Methylphenidate, and Sumatripan but has not completed enrollment.

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

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

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.

Future Research

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) follows a prioritization process to identify pediatric therapeutics and indications in need of study. Groups of experts assist with the prioritization, and there is an opportunity for public comment.

Criteria include

  • Current gaps in available evidence
  • Potential impact on children, society, and delivery of care

2018-19 Priority List

From the priority list, PTN investigators can submit a proposal to PTN. The PTN evaluates proposals, coordinates protocol development, and submits proposals to the NIH. If awarded, the PTN works with its sites to conduct the research.

PTN investigators:

Submit a study concept proposal via email.


PTN Studies

The PTN conducts Phase 1-4 trials and data-based studies across a broad range of conditions affecting pediatric patients.


Study Name Status Population Condition Study Type ID
Anesthetics and Analgesics in Children (ANA) Enrolling Children (<18 y) Anesthetic and analgesic drugs of interest (DOIs) Prospective, multi-center, open-label PK and safety profile study NCT03427736
Antibiotic safety (SCAMP) Analysis ongoing Premature infants Intra-abdominal infections Interventional NCT01994993
Anti-epileptic obesity Enrolling Obese children Epilepsy Interventional NCT02993861
Commonly used drugs during lactation and infant exposure (CUDDLE) Enrolling Breastfeeding mothers and infants Various (drugs administered regularly by physicians) Interventional NCT03511118
Digoxin Enrolling Children (<6 m) Single ventricle congenital heart disease Phase I NCT03877965
Furosemide Analysis ongoing Premature infants Bronchopulmonary dysplasia Interventional NCT02527798
Long-term Antipsychotic Pediatric Safety Trial (LAPS) Enrolling Children Mono-antipsychotic therapies Observational NCT03522168
POPS Enrolling Children (<21 y) Various (drugs administered regularly by physicians) Observational NCT01431326
Sildenafil II Enrolling Premature infants Bronchopulmonary dysplasia Phase 2 NCT03142568
Timolol Analysis ongoing Infants Infantile hemangioma Phase 2 NCT02913612


Study Name Status Population Condition Study Type ID
Acyclovir Study published on DASH; label changed Premature infants Systemic infection Phase 1 NCT00942084
Acyclovir retrospective Study published on DASH Infants Herpes simplex virus Retrospective data collection
Ampicillin Study published on DASH Infants Bacterial infections including sepsis and meningitis Secondary data analysis
Anti-staph trio Completed Premature infants Staphylococcal infections Interventional  NCT01728363
Baby TAPE Study published on DASH Newborns and young infants NA (Weight estimation tool) Interventional  NCT01507090
Baby TAPE III Study published on DASH Newborns and young infants NA (Weight estimation tool) Interventional
Caffeine Study published on DASH Premature infants and infants Bronchopulmonary dysplasia Retrospective data collection
Clindamycin obesity Clinical study report submitted to FDA Obese children Staphylococcal infections Phase 1 NCT01744730
Diuretic safety Clinical study report submitted to FDA Infants Bronchopulmonary dysplasia Retrospective observational  NA
Fluconazole safety Study published on DASH Infants Candidemia Meta-analysis NCT00734539
Hydroxyurea Clinical study report submitted to FDA Children (2-4 y) Sickle cell anemia or sickle beta-zero thalassemia Phase 2 NCT01506544
Lisinopril PK Completed; label changed Children and adolescents (2-17 y) Kidney transplant; high blood pressure Interventional NCT01491919
Lorazepam Completed; label changed Children and adolescents (3 mo-18 y) Status epilepticus (Status 1) Interventional NCT00114569
Lorazepam or diazepam Clinical study report submitted to FDA Children and adolescents (3 mo-18 y) Pediatric status epilepticus (Status 2) Interventional NCT00621478
Meropenem Completed; label changed Infants Intra-abdominal infections Interventional NCT00621192
Methadone Study published on DASH Children Opiate withdrawal Observational NCT01945736
Metronidazole Completed Premature infants Serious infection caused by anaerobic bacteria Interventional NCT01222585
Midazolam Completed Children (≥2 y) Seizures Retrospective data analysis NA
Obesity informatics Completed Children Various Systematic literature review  NA
Pantoprazole Completed Obese children GERD Phase 1 NCT02186652
Pediatrix meta-analysis Published Infants Various Meta-analysis  NA
Personal protective equipment (PPE) Completed Research doctors and nurses Evaluating impact of various PPE Interventional NA
Sildenafil Completed Premature infants Bronchopulmonary dysplasia Phase 1 NCT01670136
TAPE Clinical study report submitted to FDA Children (2-16 y) NA (Mercy Method™ for weight estimation) Observational NCT01507090
Trimethoprim-sulfamethoxazole and clindamycin Study published on DASH Children Skin and soft tissue infections Data from 3 protocols

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