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

J Perinatol. 2024 Apr;44(4):508-512. doi: 10.1038/s41372-023-01752-y. Epub 2023 Aug 16.

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.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Caffeine* / adverse effects
  • Humans
  • Hypothermia, Induced
  • Hypoxia-Ischemia, Brain* / therapy
  • Infant
  • Neuroprotection

Substances

  • Caffeine

Associated data

  • ClinicalTrials.gov/NCT03913221