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NCT Number: NCT06448780

Dose Optimization of Caffeine for HIE

This is a phase Ib, open-label, dose-validating and safety study of caffeine in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Hypoxic-Ischemic Encephalopathy Brain Diseases Brain Ischemia Cardiovascular Diseases Central Nervous System Diseases Cerebrovascular Disorders Hypoxia Hypoxia, Brain Hypoxia-Ischemia, Brain Nervous System Diseases Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Respiratory Vascular Diseases

Age range

Up to 24 hour

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

The University of North Carolina at Chapel Hill Newborn Critical Care Center, Chapel Hill, North Carolina, United States

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About this study

In a previous phase I trial (NCT03913221), the investigators characterized the pharmacokinetics (PK) of caffeine in the setting of HIE and therapeutic hypothermia using a population PK model. This is an open-label study of caffeine citrate in neonates with HIE to validate the population PK model and determine optimal dosing for HIE.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Caffeine citrate 20 mg/kg

Drug

Following loading dose of 20 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV.

Other names: Cafcit

Caffeine citrate 30 mg/kg

Drug

Following loading dose of 30 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV.

Other names: Cafcit

Primary outcomes

  1. Apparent Caffeine Clearance

    Time frame: 7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug

    Clearance is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Caffeine concentrations will be used to calculate population estimates of caffeine clearance, with inter-individual variabilty and residual variabilty .

  2. Volume of Distribution of Caffeine

    Time frame: 7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug

    Caffeine concentrations will be used to calculate population estimates of volume of distribution with inter-individual variability and residual variability.

Secondary outcomes

  1. Number of Participants with Pre-Specified Adverse Events

    Time frame: From the first dose of caffeine to 7 days following the final dose.

    Safety will be determined by the number of participants with the following: seizures requiring > 1 anti-epileptic drug, necrotizing enterocolitis defined as Bell Stage II or higher, hypoglycemia defined as point-of-care blood glucose < 30 mg/dL, and hyperglycemia defined as point-of-care blood glucose >200 mg/dL.

  2. Number of Participants with Abnormal MRI Brain Finding Score

    Time frame: During initial hospitalization, typically 3-5 postnatal days

    Preliminary effectiveness assessed using the NICHD Neonatal Research Network MRI scoring system that categorizes severity of brain injury in the Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. Abnormal MRI is defined as any score >0.

    • Score 0: Normal 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 3: Hemispheric devastation

  3. Number of Participants with Death or Neurodevelopmental Impairment

    Time frame: 18-24 months of age

    Preliminary effectiveness assessed based on death or neurodevelopmental impairment defined as: diagnosis of cerebral palsy, hearing impairment requiring hearing aids, blindness, or cognitive, language, or motor score < 85 on the Bayley Scales of Infant and Toddler Development- Fourth Edition.

Sponsors and collaborators

Lead sponsor

University of North Carolina, Chapel Hill

Other

Collaborators

  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Registry information

Official study title

Dose Optimization of Caffeine in Neonates With Hypoxic-Ischemic Encephalopathy

Important dates

Study start
2024
Primary completion
2026
Study completion
2028
First posted
Jun 7, 2024
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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