Wesley M. Jackson, Henry P. Foote, Nicole Stephenson, Steven M. Kemp, Ryan T. Moore, Christopher R. Nitkin, Dan Stewart, Gloria S. Pryhuber, John T. Berger, Ankita Shukla, Amand England, Stephanie M. Ford, Lance A. Parton, Jennifer F. Check, Mina H. Hanna, Megan Lagoski, Ramesh Krishnan, Kristen T. Leeman, Shilpa Vyas-Read, Mark L. Hudak, Anup C. Katheria, De-Ann M. Pillers, JianZhong Ji, Francis Banfro, Leif D. Nelin, Michael McCulloch, Kaashif Ahmad, Matthew M. Laughon, Christoph P. Hornik, SILDI-SAFE Study Group
University of North Carolina at Chapel Hill. Duke University. East Carolina University. Children’s Mercy-Kansas City. Norton Children’s Hospital and University of Louisville School of Medicine. University of Rochester. Children’s National Hospital. University of Arkansas for Medical Sciences and Arkansas Children’s Hospital. Ochsner Baptist Medical Center and Ochsner Children’s Hospital, Rainbow Babies and Children’s Hospital, Case Western Reserve University School of Medicine. New York Medical College and Maria Fareri Children’s Hospital at Westchester Medical Center. Boston Children’s Hospital and Harvard Medical School. Wake Forest University School of Medicine. University of Kentucky. Ann and Robert H. Lurie Children’s Hospitals of Chicago and Feinberg School of Medicine, Northwestern University. University of Tennessee Health Science Center. Emory University School of Medicine. University of Florida College of Medicine – Jacksonville. Sharp Mary Birch Hospital for Women and Newborns. University of Illinois Chicago. Dell Children’s Medical School of Central Texas. Children’s Hospital of Nevada and University Medical Center of Southern Nevada. Ohio State University. University of Virginia Children’s Hospital. Pediatrix Neonatology of Houston.
Journal of Pediatrics
J Pediatr 2026;
DOI: 10.1016/j.jpeds.2026.115147
Abstract
Objective: To describe the safety of sildenafil based on hypotension in premature infants with bronchopulmonary dysplasia (BPD).
Study design: We conducted a multicenter, randomized, double-blind, placebo-controlled, dose-escalating trial of sildenafil. Infants born < 29 weeks’ gestation and at 32-44 weeks postmenstrual age with severe BPD were randomized sequentially into 3 cohorts to receive up to 34 days of intravenous or enteral sildenafil citrate vs placebo (3:1) in a dose-escalating approach. Safety was determined by the incidence of hypotension through 28 days following the last dose of study drug. Pulmonary hypertension by serial echocardiography and daily respiratory severity scores were obtained to assess preliminary efficacy.
Results: A total of 122 infants received sildenafil (N=92) or placebo (N=30). The incidence of hypotension did not differ between the sildenafil (1/92) and placebo (0/30) groups. Serious adverse events occurred in 8% of the sildenafil group and 13% of the placebo group; retinopathy of prematurity requiring treatment in 17% and 30%, abnormal hearing results in 8% and 7%, direct hyperbilirubinemia in 4% and 3%, alanine aminotransferase elevation in 3% and 0, and escalation in respiratory support in 7% and 20%, respectively. There were no differences in daily respiratory severity scores between groups.
Conclusions: Among premature infants with severe BPD, enteral sildenafil citrate did not increase the incidence of hypotension or retinopathy of prematurity. Although we found possible differences between groups in the development of BPD-associated pulmonary hypertension diagnosed by echocardiography in high-risk infants, a larger, randomized controlled trial is needed to assess efficacy.
Category
Class III. Pulmonary Hypertension Associated with Lung Disease
Medical Therapy. Adverse Effects or Lack of Adverse Effects
Medical Therapy. Efficacy or Lack of Efficacy
Age Focus: Pediatric Pulmonary Vascular Disease
Fresh or Filed Publication: Fresh (PHresh). Less than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: No