Caffeine for Hypoxic-Ischemic Encephalopathy

University of North Carolina (UNC)

Status and phase: Completed; Phase 1

Conditions: Hypoxic-Ischemic Encephalopathy

Treatments: Drug: Caffeine Citrate 10 mg/kg; Drug: Caffeine Citrate 5 mg/kg

Study type: Interventional

Funder types: Other

Identifiers

NCT03913221

19-0348

Details and patient eligibility

About

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.

Enrollment: 17 patients

Sex: All

Ages: Under 24 hours old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented informed consent from parent or guardian
• ≥ 36 weeks gestational age at birth
• Receiving therapeutic hypothermia for a diagnosis of HIE
• Intravenous (IV) access
• Postnatal age < 24 hours

Exclusion criteria

• Receiving > 1 anti-epileptic drug for seizures
• Sustained (>4 hours) heart rate > 180 beats per minute
• Known major congenital anomaly
• Any condition which would make the participant, in the opinion of the investigator, unsuitable for the study

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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17 participants in 2 patient groups

Low Dose Caffeine (5 mg/kg)

Active Comparator group

Description:

Within 24 hours of delivery, participants will receive low dose administration of Caffeine citrate.

Treatment:

Drug: Caffeine Citrate 5 mg/kg

High Dose Caffeine (10 mg/kg)

Active Comparator group

Description:

Within 24 hours of delivery, participants will receive high dose administration of Caffeine citrate.

Treatment:

Drug: Caffeine Citrate 10 mg/kg