Sildenafil safety studied for premature infants with bronchopulmonary dysplasia

The Pediatric Trials Network (PTN), with support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is conducting an interventional study to examine the safety and efficacy of sildenafil in treating bronchopulmonary dysplasia (BPD) in premature infants.

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.

Dr. Matthew Laughon of UNC Hospitals observes infant in NICU

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.

The study, Safety of Sildenafil in Premature Infants at Risk of Bronchopulmonary Dysplasia, draws on a previous safety study conducted by the PTN from 2013 to 2016. This study enrolled 34 infants of less than 28 weeks gestational age who were receiving sildenafil to treat BPD. Health care providers administered varying doses of sildenafil and collected plasma samples to determine the optimal starting dosing for sildenafil in premature infants.

The current study is expected to enroll approximately 120 infants and will be guided by dosing data from the previous phase 1 safety study. The first study site, Golisano Children’s Hospital at the University of Rochester Medical Center in Rochester, N.Y., was activated Jan. 2 and is currently recruiting participants.

 

A busy week for the PTN sildenafil trial

The week of February 18–22 saw many milestones in the PTN sildenafil trial. On Tuesday, the first investigator’s meeting was held. By Wednesday, the trial’s first two sites had been activated — one at the Medical University of South Carolina Children’s Hospital (MUSC) and the other at the University of North Carolina–Chapel Hill. And, on Thursday, MUSC enrolled the trial’s very first patient.

Congratulations to the MUSC site team—Dr. Andrew Atz (principal investigator) and Patricia Infinger (study coordinator)—for their swift action in helping to kick off this important study!

The PTN sildenafil trial is evaluating the pharmacokinetics and safety of sildenafil in preemies suffering from bronchopulmonary dysplasia, the most common health problem associated with premature birth. Up to 20% of infants with bronchopulmonary dysplasia develop pulmonary arterial hypertension, and up to 40% of these infants die. Currently, few drugs are available to prevent bronchopulmonary dysplasia, and none can reduce death among infants with bronchopulmonary dysplasia and pulmonary arterial hypertension.

Sildenafil is approved by the FDA for the treatment of pulmonary arterial hypertension in adults, but its effectiveness in children has not been determined. In spite of this knowledge gap, sildenafil is increasingly being used off-label in premature infants at risk for or diagnosed with pulmonary arterial hypertension. The PTN hopes to establish the best dose of the drug to reduce pulmonary arterial hypertension in these fragile patients, thereby reducing the potential for harm and optimizing outcomes.

Find out more about the PTN sildenafil trial at clinicaltrials.gov.