Clinical trial NCT06448780: Dose Optimization of Caffeine for HIE
Official title: Dose Optimization of Caffeine in Neonates With Hypoxic-Ischemic Encephalopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Hypoxic-Ischemic Encephalopathy
Keywords: caffeine citrate
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2024-06-07
Enrollment: 16
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention 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.
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Apparent Caffeine Clearance
timeFrame: 7 samples will be collected after the first dose of study drug and up to 72 hours after final dose of study drug
measure: Volume of Distribution of Caffeine
timeFrame: 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:
measure: Number of Participants with Pre-Specified Adverse Events
timeFrame: From the first dose of caffeine to 7 days following the final dose.
measure: Number of Participants with Abnormal MRI Brain Finding Score
timeFrame: During initial hospitalization, typically 3-5 postnatal days
measure: Number of Participants with Death or Neurodevelopmental Impairment
timeFrame: 18-24 months of age
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill Newborn Critical Care Center
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Wesley M Jackson, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
citation: 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.