Under 24 Hours, any sex, with Hypoxic-Ischemic Encephalopathy. Patients with the condition only — healthy volunteers not accepted.
Results — posted to ClinicalTrials.gov
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
Area Under Plasma Concentration-time at Time t (AUC0-t) for CaffeinePrimary· 7 samples will be collected with the following optimal sampling windows: 0-15 minutes, 30-60 minutes, 1-3 hours, 3-6 hours, 6-12 hours, 12-18 hours, 15 minutes prior to next dose.
AUC0-t defines area under the plasma concentration-time curve (AUC) from administration to the last quantifiable concentration at time t.
AUC (0-72)
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
1137.36
± 324.96
High Dose Caffeine (10 mg/kg)
1177.94
± 134.42
AUC (0-infinity)
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
2213.26
± 540.81
High Dose Caffeine (10 mg/kg)
2768.25
± 338.06
Number of Participants With Seizures Requiring >1 Anti-Epileptic MedicationSecondary· From the first dose of caffeine to 7 days following the final dose.
As a potential complication of caffeine exposure, seizure activity requiring \>1 anti-epileptic medication is reported.
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
1
High Dose Caffeine (10 mg/kg)
0
Number of Participants With Necrotizing EnterocolitisSecondary· From the first dose of caffeine to 7 days following the final dose.
As a potential complication of caffeine exposure, the number of participants with necrotizing enterocolitis defined as Bell Stage II or III are reported.
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
0
High Dose Caffeine (10 mg/kg)
0
Number of Participants With Abnormal MRI Brain Findings Based on NICHD Neonatal Research Network ScoreSecondary· During initial hospitalization, approximately 7-14 postnatal days
The National Institute of Child Health and Human Development (NICHD) Neonatal Research Network developed and validated an MRI scoring system that categorizes severity of brain injury in the Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. A higher score is considered a worse outcome.
* Score 0: Normal T2 MRI
* Score 1A: Minimal cerebral lesions only with involvement of basal ganglia, thalamus
* Score 1B: Extensive cerebral lesions
* Score 2A: Basal ganglia thalamic, anterior or posterior limb of internal capsule, or watershed infarction
* Score 2B: 2A with cerebral lesions
*
Score 0
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
3
High Dose Caffeine (10 mg/kg)
2
Score 1A
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
2
High Dose Caffeine (10 mg/kg)
2
Score 1B
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
1
High Dose Caffeine (10 mg/kg)
3
Score 2A
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
0
High Dose Caffeine (10 mg/kg)
0
Score 2B
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
2
High Dose Caffeine (10 mg/kg)
0
Score 3
Group
Value
95% CI
Low Dose Caffeine (5 mg/kg)
0
High Dose Caffeine (10 mg/kg)
0
Adverse events — posted to ClinicalTrials.gov
Time frame: From the first dose of study intervention through 7 days after the last dose of study intervention, approximately 10 days..
Reporting threshold: 0%.
Adverse-event reports describe events observed during the trial — not all are caused by the drug.
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.
Publications & conference data
6 peer-reviewed publications reference this trial (live from Europe PMC):
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by University of North Carolina, Chapel Hill
Last refreshed: 27 March 2025
Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03913221.