Safety of Sildenafil in Premature Infants Study to Open Third Cohort Soon

Infant and adult hands

The Pediatric Trials Network (PTN) plans to open the third and final cohort (or group of study participants), in the Safety of Sildenafil in Premature Infants study in the near future. A total of 80 premature infants have been enrolled in the study so far, into the first and second study cohorts. These first and second cohorts received 0.125 mg/kg and 0.5 mg/kg of sildenafil in order to determine the safety in premature infants. 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 with BPD. However, the efficacy and safety of sildenafil in premature infants at risk for BPD is currently unknown.

Headshot of Jason Lang “More than 17,000 infants develop BPD each year so finding a drug that can help is an important public health goal. BPD can create prolonged hospitalization and in some cases, death. We hope that our study findings will help support families of infants with BPD so that there are less unknowns regarding the effectiveness of Sildenafil in treatment of infants with BPD.” said Dr. Jason Lang, the study’s Principal Investigator.

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

 

2020/2021 PTN Annual Report is Available

father and child

The 2020/2021 PTN Annual Report is now available. Click here to access.

A note from the PTN Steering Committee Chairs:

The COVID-19 pandemic has continued to challenge us in unparalleled ways and we are grateful for the commitment the Pediatric Trials Network (PTN) has exemplified in learning more about COVID as related to our youngest of patients. PTN’s Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children per Standard of Care (POP02) Study continues to make strides in supporting the treatment of younger COVID-19 patients and is currently evaluating several therapeutics to potentially treat COVID-19 pediatric patients younger than 21 years of age. In fact, POP02 has been engaged in a multi-institution, multi-study collaboration with National Institutes of Health (NIH) called The Collaboration to Assess Risk and Identify LoNG-term outcomes for Children with COVID (CARING for Children with COVID). This collaboration has worked to make de-identified data (or data that cannot be linked to a person’s identity) from children with COVID publicly available, in order to accelerate research on this important topic. The POP02 team was the first study to reach the important milestone of submitting these data and having them become available, and it is a testament to their tremendous effort and dedication. Click here for more on this. Additionally, this year PTN has released more than 20 publications and informed new label changes for clindamycin and diazepam. The Annual Review is recognition of all our hard-earned accomplishments over the past year. We look forward to all that is to come and am grateful for your commitment to determining the safest and most effective use of medications and devices in children.

Clindamycin Label Updated to Include Dosing Information for Premature and Term Infants

Mother and baby

A Pediatric Trials Network (PTN) pharmacokinetic (PK) study recently contributed to a medication label change for the drug clindamycin.

This research effort, which involved analysis data from 4 studies (Pharmacokinetics of Antistaphylococcal Antibiotics in Infants, Pharmacokinetics of Understudied Drugs Administered to Children, and Safety and Pharmacokinetics of Multiple-Dose Intravenous and Oral Clindamycin, and Antibiotic Safety in Infants With Complicated Intra-abdominal Infections), determined the pharmacokinetics in premature and term infants for treatment of staphylococcal infections.

PTN researchers measured the levels of clindamycin in each infant participant, thereby helping to determine the best dose of these drugs to treat infections in these patients. The studies found that clindamycin behaves differently in premature infants than it does in older children and adults due to the immaturity of their metabolic and kidney pathways; thus, identifying the correct dosages of drugs like clindamycin represents a critical public health need.

Thanks to this collaborative effort among PTN researchers, authorized medical providers now have appropriate guidance on how to prescribe and administer clindamycin to infants.

To learn more about the PTN studies that informed the clindamycin label change, please visit the study pages below:

PTN Research Informs Diazepam Label Change

Girl finger painting

A PTN pharmacokinetic (PK) study recently contributed to a medication label change for the drug diazepam.

This research effort, Population Pharmacokinetics and Exploratory Exposure-Response Relationships of Diazepam in Children Treated for Status Epilepticus, contributed pharmacokinetic and dosing data for the intravenous (IV) administration of diazepam.

This drug is a benzodiazepine clinically indicated in children for the management of status epilepticus and severe recurrent seizures. These seizure episodes are medical emergencies and can result in long-term adverse consequences and even mortality in children.

Pharmacokinetic and dosing data for the usage of diazepam in children 3 months of age up to 17 years of age has now been incorporated into the FDA drug label as a result of data analyzed in this PTN study.

Thanks to this collaborative effort among PTN researchers, authorized medical providers now have appropriate guidance on how to prescribe and administer diazepam to children with status epilepticus and severe recurrent seizures.

ANA Study Updates Protocol to Include New Medications

Two children standing on bridge

The PTN’s Anesthesia and Analgesics in Children (ANA) study has updated its study protocol to include new medications to be studied in pediatric populations. These new medications being studied, known as drugs of interest (DOI), include morphine, oxycodone, and ketamine. Although often prescribed by providers for anesthetic and analgesic (or pain relief) reasons, the safety, efficacy, and dosing information of these medications have not been established in pediatric populations.

The drug morphine is an analgesic, or opiate drug used for patients with severe pain. While this medication is approved to be prescribed for adults, for children it is often prescribed off-label by doctors or authorized medical professionals to treat symptoms of pain. Morphine is the most commonly prescribed opiate pain reliever in children, despite not having enough safety and efficacy data to establish FDA-approved dosing guidelines. Researchers will be studying this medication when administered through an intravenous line to inform guidelines for pediatric dosing.

Oxycodone is another new DOI being researched in the PTN ANA study. This drug is also an analgesic drug popularly prescribed off-label by prescribers for severe pain management in children and currently has no safety and efficacy data for dosing in children under the age of 18. Like morphine, oxycodone is an alternative treatment prescribed when previously prescribed pain medications are shown to be ineffective. Researchers will be studying this medication when administered via oral tablet and oral liquid solution.

An anesthetic drug, ketamine, was also added to this pharmacokinetic (PK) study. Ketamine is approved for adults as an introductory anesthetic drug prior to receiving further anesthetics for diagnostic and surgical procedures. This is another drug given off-label as an anesthetic in children undergoing invasive medical procedures. Although data in adults suggests this anesthetic produces minimal side effects, the correct and safe dose for children under the age of 16 is unknown. With support of Duke University’s Population Health Sciences Department, the PTN will also be testing a new tool to measure the sedation level in children to see how this new tool compares to prior measurement tools.

The PTN is thrilled to add these medications to the ANA study, which has enrolled participants aged 2 to 17 who currently receive anesthetic or analgesic drugs as part of their routine care. Once this study is completed and data are analyzed, the PTN will submit results to the Food and Drug Administration (FDA) to change the label of the medications studied and establish information and dosing guidelines for children.

LAPS Trial Meets Study and Sub-Study Milestones

Child writing with pencil

The PTN Long-term Antipsychotic Pediatric Safety (LAPS) Trial, which aims to assess the long-term health of risperidone and aripiprazole in children, has enrolled more than 500 children in the main study. Risperidone and aripiprazole have been shown to be effective for the treatment of conditions such as schizophrenia and bipolar disorder in adults and children. However, 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. Regardless of indication, little is known about the long-term health risks and quality-of-life benefits for their use in children.

In addition to the main study, the team has established a sub-study registry that will continue to collect height and weights, from home, via the Pattern Health mobile app. This will allow for continued longitudinal assessment of pathologic weight change associated with these antipsychotics.  In addition to the use of the app, parents of participants will also complete quality of life questionnaires, every six months, for their children participating in the sub-study. The team has enrolled more than 250 children in the sub-study portion of LAPS.

The ultimate goal of the both the main study and sub-study is to provide long-term 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.

PTN Receives Funding to Study Device Used to Treat Overactive Bladder

child in bathroom

The Pediatric Trials Network (PTN) is thrilled to announce the Network has received funding from the Best Pharmaceuticals for Children Act (BPCA) to study a device to treat Overactive Bladder (OAB) in pediatric patients. The project is planned as a collaboration with industry partner Laborie Medical Technologies Corp, who will provide devices for the study.

Overactive bladder affects up to 47% of children and can be influenced by conditions such as recurrent urinary tract infection (UTI), psychiatric & developmental disorders, and obesity. This condition can negatively impact the quality of life of children and exacerbate or lead to other chronic health conditions. The most common medication therapies are oxybutynin (Ditropan) and solifenacin (Vesicare), and are approved by the Food and Drug Administration (FDA) in children and adults. However, there is concern that there can be long-term side effects of oxybutynin, which includes memory problems and possible development of dementia in late adulthood.

The device is a posterior tibial nerve stimulation (PTNS), called the Urgent PC System, and will be used to treat OAB. This device is approved to treat OAB in adults, however there is not enough safety and efficacy data yet to approve it as a treatment for children with the condition. To prescribe PTNS devices, such as the Urgent PC system, into future OAB therapies for children, the PTN will test the safety and efficacy of the device in children ages 5 to 21 years old. Safety events or side effects such as electrode site reaction, electrode site infection, and residual will be tested and data will be validated via the Vancouver Dysfunctional Elimination Syndrome (VDES) questionnaire.

Testing the Urgent PC system as a PTNS device therapy in children with OAB will demonstrate the PTN’s ability to study medical device therapies. Future PTN medical device studies may be possible after the potential approval of the Urgent PC system and PTNS to the FDA from data collected during this study by the Network.

PTN Makes COVID Data Publically Available As Part of CARING Collaboration

Young child wearing face mask

The PTN Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children per Standard of Care (POP02) study team has been engaged in a multi-institution, multi-study collaboration with National Institutes of Health (NIH) called The Collaboration to Assess Risk and Identify LoNG-term outcomes for Children with COVID (CARING for Children with COVID). This collaboration has worked to make de-identified data (or data that cannot be linked to a person’s identity) from children with COVID publicly available, in order to accelerate research on this important topic.

The POP02 team was the first study to reach the important milestone of submitting these data and having them become available, and it is a testament to their tremendous effort and dedication.

Congrats to the POP02 team! To learn more about POP02, visit the POP02 study page.

Geaux Team – Louisiana Site Remains Committed Amidst Challenges

ochsner-baptist

Many clinical sites that are contributing to the enrollment of Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children per Standard of Care Study (POP02) are facing unique challenges presented by the COVID-19 Delta surge. However, Ochsner Baptist Medical Center (OBMC), in New Orleans, Louisiana has faced more unique challenges than most.

In addition to the COVID-19 pandemic, OBMC has dealt with challenges presented by Hurricane Ida that made landfall in late August. Hurricane Ida is the second-most damaging and intense hurricane to make landfall in the state of Louisiana. The residents of Louisiana are still recovering from the impacts of the devastating storm.

However, the POP02 team at OBMC has continued to enroll participants in POP02 and contribute to the overall steady enrollment and milestone completion for the study. Pictured below are Brooke Langley, Neonatal Intensive Care Unit (NICU) Clinical Research Registered Nurse (L) and Rafael Velasquez, Senior Clinical Research Coordinator (R). Brooke and Rafael are two key contributors to the POP02 efforts taking place in Louisiana.

LA POP02 Site

The POP02 coordinating team is immensely grateful for the steadfast commitment of people like Brooke, Rafael, and all those that are unifying to end COVID-19, and ultimately improve child health.

To learn more about the POP02 study, read our latest announcement highlighting study enrollment.

POP02 Continues to Enroll Rapidly and Meet Study Milestones

This year, the Pediatric Trial Network (PTN) has now enrolled over 600 pediatric participants into its Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs Administered to Children per Standard of Care (POP02) Study, which includes SARS-CoV-2 positive participants.

As of September 2021, there are more than 400 SARS-CoV-2 participants and over 100 participants with multisystem inflammatory syndrome in children (MIS-C). Pediatric COVID-19 rates have been increasing since July 2021, as seen in the graphic below from the American Academy of Pediatrics. This graphic represents the need for pediatric pharmacokinetic research such as the PTN POP02 study.

POP02 COVID-19 Data

By enrolling pediatric participants that have tested positive for the virus, which causes COVID-19 illness, researchers will be able to evaluate combinations of drug therapies to treat children affected by acute COVID-19 illness and/or MIS-C. This condition resulting from COVID-19 illness causes inflammation of different body parts, including essential organs. So far, 95 participants have been enrolled into POP02 that have MIS-C, an illness that can be developed in children after contracting SARS-CoV-2, the virus that causes COVID-19.

The POP02 study also includes nearly 15 participants with Down Syndrome (DS). Enrolling and including patients with Down Syndrome helps achieve the goals put forth by the INCLUDE project. The purpose of the INCLUDE project is to enhance clinical trial support for medication usage in children with DS and to promote training for clinical trials in those with DS for PTN and DS clinicians. By enrolling these pediatric participants and others in POP02, PTN researchers will be able to provide dosing and safety data for medications essential to the treatment of patients with a variety of health conditions.