Hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia is common and often fatal.
Therapeutic hypothermia reduces mortality and morbidity in infants with HIE. Even with the
widespread use of therapeutic hypothermia, ~60% of infants with HIE die or have
neurodevelopmental impairment. As a result, there is an urgent, unmet public health need to
develop adjuvant therapies to improve survival and neurodevelopmental outcomes in this
population.
Caffeine may offer neuroprotection for infants with HIE by blocking adenosine receptors in
the brain and reducing neuronal cell death. In animal models of HIE, caffeine reduces white
matter brain injury. Drugs in the same class as caffeine (i.e., methylxanthines) have been
shown to be protective against acute kidney injury in the setting of HIE. However, their
safety and efficacy have not been studied in the setting of therapeutic hypothermia and their
effect on neurological outcomes is not known. Since these drugs reduce injury to the kidney
in infants with HIE, they may also reduce injury to the brain.
This phase I study will evaluate the pharmacokinetics, safety, and preliminary effectiveness
of caffeine as an adjuvant therapy to improve neurodevelopmental outcomes in infants with
HIE.