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Safety of sildenafil in extremely premature infants: a phase I trial

Journal of Perinatology volume 42, pages 31–36 (2022)Cite this article

Subjects

Abstract

Objective

To characterize the safety of sildenafil in premature infants.

Study design

A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (cohort 2). Safety was evaluated based on adverse events (AEs), transaminase levels, and mean arterial pressure monitoring.

Results

Twenty-four infants in cohort 1 (n = 25) received enteral sildenafil. In cohort 2, infants received a single IV sildenafil dose of 0.25 mg/kg (n = 7) or 0.125 mg/kg (n = 2). In cohort 2, there was one serious AE related to study drug involving hypotension associated with a faster infusion rate than specified by the protocol. There were no AEs related to elevated transaminases.

Conclusion

Sildenafil was well tolerated by the study population. Drug administration times and flush rates require careful attention to prevent infusion-related hypotension associated with faster infusions of IV sildenafil in premature infants.

Clinical trial

ClinicalTrials.gov Identifier: NCT01670136.

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Fig. 1: Change from baseline Mean Arterial Pressure (MAP) over time following start of IV sildenafil infusion.

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Acknowledgements

Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee: Danny Benjamin, Edmund Capparelli, Erin Campbell, Greg Kearns, Ian Paul, Julie Autmizguine, Kanecia Zimmerman, Kelly Wade, Perdita Taylor-Zapata, Peter Hoffmann, Ravander Anand, Tom Green.

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Grant/Award Number: HHSN275201000003I.

Author information

Authors and Affiliations

  1. Department of Pediatrics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Wesley Jackson & Matthew M. Laughon

  2. Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Daniel Gonzalez

  3. Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA

    P. Brian Smith, Chi D. Hornik, Michael Cohen-Wolkowiez & Christoph P. Hornik

  4. Duke Clinical Research Institute, Durham, NC, USA

    P. Brian Smith, Chi D. Hornik, Mary Mills, Michael Cohen-Wolkowiez & Christoph P. Hornik

  5. Division of Neonatology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Namasivayam Ambalavanan

  6. Department of Pediatrics, Medical University of South Carolina Children’s Hospital, Charleston, SC, USA

    Andrew M. Atz

  7. Division of Neonatal‐Perinatal Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Gregory M. Sokol

  8. University of Louisville Norton Children’s Hospital, Louisville, KY, USA

    Dan Stewart

  9. Kings County Hospital Center/SUNY Downstate Medical Center, Brooklyn, NY, USA

    Gratias Mundakel

  10. Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Brenda B. Poindexter

  11. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

    Shawn K. Ahlfeld

  12. The Emmes Company, LLC, Rockville, MD, USA

    Karen Martz

Authors
  1. Wesley Jackson
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  2. Daniel Gonzalez
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  3. P. Brian Smith
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  4. Namasivayam Ambalavanan
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  16. Matthew M. Laughon
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Consortia

Best Pharmaceuticals for Children Act—Pediatric Trials Network Steering Committee

Contributions

DG, PBS, NA, AMA, GMS, DS, GM, BBP, SKA, MM, MCW, CPH, MML: Designed the study and enrolled infants in the trial. KM: Performed the analysis. WJ: Wrote the first draft of the manuscript. DG, PBS, NA, AMA, GMS, CDH, DS, GM, BBP, SKA, MM, MCW, KM, CPH, and MML: Reviewed and made significant edits to the manuscript.

Corresponding author

Correspondence to Wesley Jackson.

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The authors declare no competing interests.

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Jackson, W., Gonzalez, D., Smith, P.B. et al. Safety of sildenafil in extremely premature infants: a phase I trial. J Perinatol 42, 31–36 (2022). https://doi.org/10.1038/s41372-021-01261-w

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