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A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy

Journal of Perinatology volume 44, pages 508–512 (2024)Cite this article

Subjects

Abstract

Objective

Caffeine provides neuroprotection following hypoxic-ischemic injury in animals. We characterized the safety of escalating doses of caffeine in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia.

Study design

Phase I trial of infants undergoing therapeutic hypothermia for HIE receiving IV caffeine 20 mg/kg followed by up to two daily doses of 5 mg/kg (n = 9) or 10 mg/kg (n = 8). Safety was evaluated based on adverse events and frequency of pre-specified outcomes compared to data from the Whole-Body Hypothermia for HIE trial (Shankaran, 2005).

Results

Twelve of 17 (71%) infants had ≥1 adverse event during the study period. The frequency of clinical outcomes related to HIE were not statistically different from outcomes in infants receiving hypothermia in the Whole-Body Hypothermia for HIE trial.

Conclusion

Caffeine administration was well tolerated. A larger study is required to determine the optimal dose and evaluate drug safety and efficacy.

Clinical trial

ClinicalTrials.gov Identifier: NCT03913221.

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Funding

Thrasher Research Fund Early Career Award for Dr. Jackson (#14934), and a mentoring award from the National Heart, Lung, and Blood Institute for Dr. Laughon (1K24HL143283).

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

    Rachel G. Greenberg

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

    Rachel G. Greenberg

  5. Department of Radiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Yueh Z. Lee

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  1. Wesley Jackson
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  4. Yueh Z. Lee
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  5. Matthew M. Laughon
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Contributions

WJ, DG, MML, and RGG designed the study. WJ enrolled patients in the trial, performed the safety analysis, and wrote the first draft of the manuscript. YZL reviewed all brain MRIs. DG, RGG, YZL, and MML reviewed and made significant edits to the manuscript.

Corresponding author

Correspondence to Wesley Jackson.

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Competing interests

WJ, MML, and YZL have no conflicts of interest to disclose. DG performs consulting services for Tellus Therapeutics unrelated to the content of this article. RGG has received support from industry for research services (https://dcri.org/about-us/conflict-of-interest/).

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Jackson, W., Gonzalez, D., Greenberg, R.G. et al. A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy. J Perinatol 44, 508–512 (2024). https://doi.org/10.1038/s41372-023-01752-y

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