Dose Optimization of Caffeine for HIE

April 6, 2026 updated by: University of North Carolina, Chapel Hill

Dose Optimization of Caffeine in Neonates With Hypoxic-Ischemic Encephalopathy

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Estimated)

16

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • The University of North Carolina at Chapel Hill Newborn Critical Care Center
        • Contact:
      • Wilmington, North Carolina, United States, 28401
        • Recruiting
        • Novant Health New Hanover Regional Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Lower loading dose (20 mg/kg)
Within 24 hours after delivery, participants will receive a loading dose of 20 mg/kg caffeine citrate IV.
Drug: Caffeine citrate 20 mg/kg
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
Active Comparator: Higher loading dose (30 mg/kg)
Within 24 hours after delivery, participants will receive a loading dose of 30 mg/kg caffeine citrate IV.
Drug: Caffeine citrate 30 mg/kg
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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 .
7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug
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.
7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
From the first dose of caffeine to 7 days following the final dose.
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
During initial hospitalization, typically 3-5 postnatal days
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.
18-24 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of North Carolina, Chapel Hill

Collaborators

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

Investigators

  • Principal Investigator: Wesley M Jackson, MD, MPH, University of North Carolina, Chapel Hill

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 26, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

June 3, 2024

First Submitted That Met QC Criteria

June 3, 2024

First Posted (Actual)

June 7, 2024

Study Record Updates

Last Update Posted (Actual)

April 7, 2026

Last Update Submitted That Met QC Criteria

April 6, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 24-0654
  • 1K23HD111623-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

IPD Sharing Time Frame

Beginning 9 months and ending 36 months following article publication.

IPD Sharing Access Criteria

Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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