Hypoxic-Ischemic EncephalopathyPhase 1NCT06448780
Dose Optimization of Caffeine for HIE
A Phase 1 study testing Caffeine citrate 20 mg/kg and Caffeine citrate 30 mg/kg in people with Hypoxic-Ischemic Encephalopathy, run by University of North Carolina, Chapel Hill at 2 sites in United States.
Trial summary
This is a phase Ib, open-label, dose-validating and safety study of caffeine in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia. Read more about this study
- Who is it for?
- Ages Up to 24 hours
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy
- What is being tested?
- Caffeine citrate 20 mg/kg and Caffeine citrate 30 mg/kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesUnited States
- Study dates
- 26 Jul 2024to Jul 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 24 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- Receiving > 1 anti-epileptic drug for seizures
- Sustained (>4 hours) heart rate > 180 beats per minute
- Known major congenital anomaly
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The University of North Carolina at Chapel Hill Newborn Critical Care Center
Chapel Hill, North Carolina, 27599
Novant Health New Hanover Regional Medical Center
Wilmington, North Carolina, 28401
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Being tested
- Caffeine citrate 20 mg/kg, Caffeine citrate 30 mg/kg
- Keywords
- caffeine citrate
- Medical subject headings
- Hypoxia-Ischemia, Brain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Caffeine citrate 20 mg/kgDrug
Also called Cafcit
Following loading dose of 20 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV.
Caffeine citrate 30 mg/kgDrug
Also called Cafcit
Following loading dose of 30 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV.
| Study group | Role | What they receive |
|---|---|---|
| Lower loading dose (20 mg/kg) | Active comparator | Within 24 hours after delivery, participants will receive a loading dose of 20 mg/kg caffeine citrate IV. Receives: Drug: Caffeine citrate 20 mg/kg |
| Higher loading dose (30 mg/kg) | Active comparator | Within 24 hours after delivery, participants will receive a loading dose of 30 mg/kg caffeine citrate IV. Receives: Drug: Caffeine citrate 30 mg/kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Apparent Caffeine Clearance
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 .
Measured: 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
Caffeine concentrations will be used to calculate population estimates of volume of distribution with inter-individual variability and residual variability.
Measured: 7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug
Secondary outcomes (3)
Number of Participants with Pre-Specified Adverse Events
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.
Measured: From the first dose of caffeine to 7 days following the final dose.
Number of Participants with Abnormal MRI Brain Finding Score
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
Measured: During initial hospitalization, typically 3-5 postnatal days
Number of Participants with Death or Neurodevelopmental Impairment
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.
Measured: 18-24 months of age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2024
- Study start26 Jul 2024
- Primary completion25 Jun 2026
- Study completionJul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The first cohort of 8 infants will receive a lower loading dose of caffeine. Following a safety review, an additional 8 infants will receive a higher loading dose.
- Masking
- None (open label)
- Enrolment
- 16 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Sponsor
- Investigators
- Wesley M Jackson, MD, MPH, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06448780
- Sponsor's protocol ID
- 24-0654
- Other IDs
- 1K23HD111623-01
- Status last verified
- Jun 2026
- First submitted
- 3 Jun 2024
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Shankaran S, McDonald SA, Laptook AR, Hintz SR, Barnes PD, Das A, Pappas A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2015 Nov;167(5):987-93.e3. doi: 10.1016/j.jpeds.2015.08.013. Epub 2015 Sep 16.
PubMed 26387012Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL. Neonatal Acute Kidney Injury. Pediatrics. 2015 Aug;136(2):e463-73. doi: 10.1542/peds.2014-3819. Epub 2015 Jul 13.
PubMed 26169430Jackson W, Gonzalez D, Greenberg RG, Lee YZ, Laughon MM. A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy. J Perinatol. 2024 Apr;44(4):508-512. doi: 10.1038/s41372-023-01752-y. Epub 2023 Aug 16.
PubMed 37587184
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Optimization of Caffeine in Neonates With Hypoxic-Ischemic Encephalopathy
- ClinicalTrials.gov ID
- NCT06448780
- Acronym / sponsor ID
- 24-0654
- Conditions
- Hypoxic-Ischemic Encephalopathy
- Keywords
- caffeine citrate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 16 participants (estimated)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 26 Jul 2024 (actual)
- Primary completion
- 25 Jun 2026 (actual)
- Study completion
- Jul 2028 (estimated)
- First posted
- 7 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase Ib, open-label, dose-validating and safety study of caffeine in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The first cohort of 8 infants will receive a lower loading dose of caffeine. Following a safety review, an additional 8 infants will receive a higher loading dose.
| Arm | Type | Receives |
|---|---|---|
| Lower loading dose (20 mg/kg) | Active comparator | Drug: Caffeine citrate 20 mg/kgWithin 24 hours after delivery, participants will receive a loading dose of 20 mg/kg caffeine citrate IV. |
| Higher loading dose (30 mg/kg) | Active comparator | Drug: Caffeine citrate 30 mg/kgWithin 24 hours after delivery, participants will receive a loading dose of 30 mg/kg caffeine citrate IV. |
Who may qualify
- Ages
- Up to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- Receiving > 1 anti-epileptic drug for seizures
- Sustained (>4 hours) heart rate > 180 beats per minute
- Known major congenital anomaly
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Caffeine citrate 20 mg/kgAlso: CafcitFollowing loading dose of 20 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV. | Drug | Lower loading dose (20 mg/kg) |
| Caffeine citrate 30 mg/kgAlso: CafcitFollowing loading dose of 30 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV. | Drug | Higher loading dose (30 mg/kg) |
Primary outcome
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 .
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.
3 secondary outcomes
Number of Participants with Pre-Specified Adverse Events
Time frame: 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
Number of Participants with Death or Neurodevelopmental Impairment
Time frame: 18-24 months of age
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
- Background: PubMed 26387012Shankaran S, McDonald SA, Laptook AR, Hintz SR, Barnes PD, Das A, Pappas A, Higgins RD; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2015 Nov;167(5):987-93.e3. doi: 10.1016/j.jpeds.2015.08.013. Epub 2015 Sep 16.
- Background: PubMed 26169430Selewski DT, Charlton JR, Jetton JG, Guillet R, Mhanna MJ, Askenazi DJ, Kent AL. Neonatal Acute Kidney Injury. Pediatrics. 2015 Aug;136(2):e463-73. doi: 10.1542/peds.2014-3819. Epub 2015 Jul 13.
- Background: PubMed 37587184Jackson W, Gonzalez D, Greenberg RG, Lee YZ, Laughon MM. A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy. J Perinatol. 2024 Apr;44(4):508-512. doi: 10.1038/s41372-023-01752-y. Epub 2023 Aug 16.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Hypoxic-Ischemic Encephalopathy
Not yet recruiting
Levetiracetam as an Adjuvant Therapy to Hypothermia in Neonatal Asphyxia
Hypoxic Ischemic Encephalopathy of Newborn, Neuro-protection
Recruiting
Minimal Sedation Versus Standard Continuous Sedation After Out-of-Hospital Cardiac Arrest
Out-of-Hospital Cardiac Arrest, Hypoxic-Ischemic Brain Injury
RecruitingPhase 2
The PROTECT-HIE Pilot Trial
Hypoxic-ischemic Encephalopathy (HIE)
Recruiting
Neuro-MoD: Neuroplasticity With Motor Development
Perinatal Brain Injury
RecruitingPhase 2
A Dose Escalation Study of Levetiracetam in the Treatment of Neonatal Seizures
Neonatal Seizure, Neonatal Encephalopathy
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wesley M Jackson, MD, MPH principal investigator
University of North Carolina, Chapel Hill
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Caffeine citrate 20 mg/kg and Caffeine citrate 30 mg/kg in people with Hypoxic-Ischemic Encephalopathy, run by University of North Carolina, Chapel Hill at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06448780, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.