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Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial.

Publication ,  Journal Article
Lang, JE; Hornik, CD; Martz, K; Jacangelo, J; Anand, R; Greenberg, R; Hornik, C; Zimmerman, K; Smith, PB; Benjamin, DK; Laughon, M ...
Published in: Contemp Clin Trials Commun
December 2022

Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to alveolar simplification, impaired alveolar-capillary development, interstitial fibrosis, and often pulmonary hypertension. BPD is the most common pulmonary sequela of prematurity and is often fatal; however, there remains no FDA-approved therapies to treat or prevent BPD. Sildenafil is increasingly used off-label in premature infants despite scant safety and efficacy data. Sildenafil reduces lung injury and preserves normal vasculature in preclinical models, and improves outcomes in children with pulmonary hypertension, and thus is a promising candidate for BPD. Following phase I studies, we developed the phase II SIL02 trial to describe the safety, pharmacokinetics and preliminary effectiveness of intravenous and enteral sildenafil in premature infants at risk for BPD. SIL02 is a randomized, double-blind, placebo-controlled, 3-cohort, sequential dose-escalating trial of enteral or intravenous (IV) sildenafil dosed every 8 h for up to 34 days. The target IV doses were 0.125, 0.5 and 1 mg/kg/dose in cohorts 1, 2 and 3, respectively; while the enteral doses will be double the IV doses. Eligible infants must be < 29 weeks' gestation at birth and requiring respiratory support at 7-28 days' postnatal age. Adverse events and preliminary effectiveness will be compared by treatment group. Using the final population PK model, empirical Bayesian estimates will be generated for each patient. Preliminary effectiveness will be measured by the incidence of moderate to severe BPD or death at 36 weeks and change in the BPD risk estimation.

Duke Scholars

Published In

Contemp Clin Trials Commun

DOI

EISSN

2451-8654

Publication Date

December 2022

Volume

30

Start / End Page

101025

Location

Netherlands

Related Subject Headings

  • 32 Biomedical and clinical sciences
 

Citation

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Lang, J. E., Hornik, C. D., Martz, K., Jacangelo, J., Anand, R., Greenberg, R., … Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee, . (2022). Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial. Contemp Clin Trials Commun, 30, 101025. https://doi.org/10.1016/j.conctc.2022.101025
Lang, Jason E., Chi D. Hornik, Karen Martz, Juliana Jacangelo, Ravinder Anand, Rachel Greenberg, Christoph Hornik, et al. “Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial.Contemp Clin Trials Commun 30 (December 2022): 101025. https://doi.org/10.1016/j.conctc.2022.101025.
Lang JE, Hornik CD, Martz K, Jacangelo J, Anand R, Greenberg R, et al. Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial. Contemp Clin Trials Commun. 2022 Dec;30:101025.
Lang, Jason E., et al. “Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial.Contemp Clin Trials Commun, vol. 30, Dec. 2022, p. 101025. Pubmed, doi:10.1016/j.conctc.2022.101025.
Lang JE, Hornik CD, Martz K, Jacangelo J, Anand R, Greenberg R, Hornik C, Zimmerman K, Smith PB, Benjamin DK, Laughon M, Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee. Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial. Contemp Clin Trials Commun. 2022 Dec;30:101025.
Journal cover image

Published In

Contemp Clin Trials Commun

DOI

EISSN

2451-8654

Publication Date

December 2022

Volume

30

Start / End Page

101025

Location

Netherlands

Related Subject Headings

  • 32 Biomedical and clinical sciences