Dose Optimization of Caffeine for HIE

Hypoxic-Ischemic Encephalopathy Clinical Trial

Official title:

Dose Optimization of Caffeine in Neonates With Hypoxic-Ischemic Encephalopathy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06448780
• Other study ID #: 24-0654
• Secondary ID: 1K23HD111623-01
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: November 2024
• Est. completion date: November 2028

Study information

• Verified date: June 2024
• Source: University of North Carolina, Chapel Hill
• Contact: Wesley M Jackson, MD, MPH
• Phone: 984-215-3449
• Email: wesley.jackson[@]unc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 16
• Est. completion date: November 2028
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	The University of North Carolina at Chapel Hill Newborn Critical Care Center	Chapel Hill	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
University of North Carolina, Chapel Hill	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	From the first dose of caffeine to 7 days following the final dose.
Secondary	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	During initial hospitalization, typically 3-5 postnatal days
Secondary	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.	18-24 months of age