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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
First received
Last updated
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
Health authority
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

Study Design


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
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