Dose Optimization of Caffeine for HIE

Phase 1Active Not RecruitingNCT06448780

University of North Carolina, Chapel Hill16 enrolled

Overview

This is a phase Ib, open-label, dose-validating and safety study of caffeine in neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia.

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypoxic-Ischemic Encephalopathy

Interventions

Caffeine citrate 20 mg/kgDRUG

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

Following loading dose of 30 mg/kg of caffeine citrate IV, participants will receive 2 daily doses of 10 mg/kg caffeine citrate IV.

Eligibility

Sex: ALLMax age: 24 Hours

Medical Language ↔ Plain English

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

Locations (2)

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

Chapel Hill, North Carolina, United States

Novant Health New Hanover Regional Medical Center

Wilmington, North Carolina, United States

Outcomes

Primary Outcomes

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 .

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

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.

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

Secondary Outcomes

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.

Time frame: 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

Time frame: During initial hospitalization, typically 3-5 postnatal days

Data from ClinicalTrials.gov

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