Dose Optimization of Caffeine for HIE

NCT06448780 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 24-06541K23HD111623-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Hypoxic-Ischemic Encephalopathy

Keywords

caffeine citrate

Outcome Measures

Primary Outcomes (2)

• 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 .

  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.

  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

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

• Number of Participants with Abnormal MRI Brain Finding Score

  During initial hospitalization, typically 3-5 postnatal days

• Number of Participants with Death or Neurodevelopmental Impairment

  18-24 months of age

Study Arms (2)

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.

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.

Drug: Caffeine citrate 30 mg/kg

Interventions

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.

Also known as: Cafcit

Lower loading dose (20 mg/kg)

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.

Also known as: Cafcit

Higher loading dose (30 mg/kg)

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Receiving \> 1 anti-epileptic drug for seizures
• Sustained (\>4 hours) heart rate \> 180 beats per minute
• Known major congenital anomaly

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (2)

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

Chapel Hill, North Carolina, 27599, United States

RECRUITING

Novant Health New Hanover Regional Medical Center

Wilmington, North Carolina, 28401, United States

NOT YET RECRUITING

Related Publications (3)

• 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.

  PMID: 26387012 BACKGROUND

• Selewski 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.

  PMID: 26169430 BACKGROUND

• Jackson 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.

  PMID: 37587184 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

Interventions

caffeine citrate

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Wesley M Jackson, MD, MPH

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wesley M Jackson, MD, MPH

CONTACT

984-215-3449; wesley.jackson@unc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 3, 2024
• First Posted: June 7, 2024
• Study Start: July 26, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): November 1, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• 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.

Locations

US (2)