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A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants

Journal of Perinatology volume 34, pages 705–710 (2014)Cite this article

Subjects

Abstract

Objective:

Bronchopulmonary dysplasia (BPD) is the most common cause of pulmonary morbidity in premature infants and is associated with life-long morbidities. Developing drugs for the prevention of BPD would improve public health. We sought to determine characteristics of favorable randomized controlled trials (RCTs) of drugs for BPD prevention.

Study Design:

We searched MEDLINE and EMBASE from 1992 to 2014 using the MeSH terms ‘BPD’ and ‘respiratory distress syndrome, newborn’. We included a Cochrane Library search to ensure inclusion of all available RCTs. We identified RCTs with BPD as a primary or secondary outcome and determined the definition of BPD used by the study. We determined whether a phase I or phase II study—to determine drug safety, efficacy or optimal dose—was performed before the RCT. Finally, we searched the Cochrane Library for meta-analyses for each drug and used the results of available meta-analyses to define a favorable versus unfavorable RCT.

Result:

We identified 2026 articles; 47 RCTs met our inclusion criteria encompassing 21 drugs; 5 of the drugs reduced the incidence of BPD. We found data from phase I or II studies for 16 of the drugs, but only 1 demonstrated a reduction of BPD.

Conclusion:

The majority of the drugs studied in RCTs failed to reduce the incidence of BPD. Performing early-phase studies before phase III trials might provide necessary information on drugs and drug doses capable of preventing BPD, thus informing the development of future RCTs.

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Acknowledgements

We thank and acknowledge Kathleen McGraw for her expertise in assisting in the development of the literature search. Dr Cohen-Wolkowiez receives support for research from the National Institutes of Health (NIH) (1K23HD064814), the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the Food and Drug Administration (1U01FD004858-01), the Biomedical Advanced Research and Development Authority (BARDA) (HHSO100201300009C), the nonprofit organization Thrasher Research Fund (http://www.thrasherresearch.org) and from industry for drug development in adults and children (http://www.dcri.duke.edu/research/coi.jsp). Dr Smith receives salary support for research from the NIH, the US Department of Health and Human Services and the National Center for Advancing Translational Sciences of the NIH (DHHS-1R18AE000028-01, HHSN267200700051C, HHSN275201000003I and UL1TR001117); he also receives research support from industry for neonatal and pediatric drug development (http://www.dcri.duke.edu/research/coi.jsp). Dr Laughon receives support from the US government for his work in pediatric and neonatal clinical pharmacology (Government Contract HHSN267200700051C, PI: Benjamin under the Best Pharmaceuticals for Children Act) and from NICHD (1K23HL092225-01); he also receives support from Astellas, Pfizer, Abbvie and Discovery Laboratories for his work on data safety monitoring boards and consulting. This work was supported by a grant from the Doris Duke Charitable Foundation to UNC–Chapel Hill School of Medicine to fund clinical research fellow Kristyn S Beam. The project described was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, through grant award numbers UL1TR000083 and UL1TR001117. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

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Authors and Affiliations

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

    K S Beam, S Aliaga & M M Laughon

  2. Indiana University, Indianapolis, IN, USA

    S K Ahlfeld

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

    M Cohen-Wolkowiez, P B Smith & M M Laughon

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  1. K S Beam
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Correspondence to M M Laughon.

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Beam, K., Aliaga, S., Ahlfeld, S. et al. A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants. J Perinatol 34, 705–710 (2014). https://doi.org/10.1038/jp.2014.126

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