Dexmedetomidine Pharmacokinetics in Neonates During Therapeutic Hypothermia

Early Phase 1CompletedNCT02529202

Seattle Children's Hospital7 enrolled

Overview

The goal of this proposal is to profile the pharmacokinetics of dexmedetomidine in newborns ≥36 weeks post-menstrual age during therapeutic hypothermia for hypoxic-ischemic encephalopathy.

The goal of this proposal is to determine the pharmacokinetics (PK) of dexmedetomidine (DEX) in newborns in the neonatal intensive care unit (NICU) receiving therapeutic hypothermia (TH) for moderate to severe hypoxic-ischemic encephalopathy (HIE). In newborns with HIE, TH for 72 hours is the standard therapy to mitigate brain damage. Most HIE patients receive mechanical ventilation during TH and are thus sedated with morphine. Unfortunately, morphine has negative side effects and does not specifically prevent shivering. Prevention of shivering is critical to success of TH, as shivering negates cooling. DEX is a particularly promising alternative sedative because it does prevent shivering and is already used in NICUs for sedation and pain management. In newborns, DEX PK data in the setting of TH is not available and needs to be determined to properly dose DEX for HIE patients.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypoxic-ischemic Encephalopathy

Interventions

DexmedetomidineDRUG

Dexmedetomidine infusion

Eligibility

Sex: ALLMin age: 1 HourMax age: 1 Day

Medical Language ↔ Plain English

Inclusion Criteria: 1. Newborns 36 weeks gestation or older with moderate to severe hypoxic-ischemic encephalopathy identified and treated with therapeutic hypothermia in the Seattle Children's Hospital neonatal intensive care unit. 2. Cooled infants who are initially intubated and mechanically ventilated. 3. Infants anticipated to require 72 hrs of continuous sedation and/or treatment to prevent shivering. 4. Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the informed consent document approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC). Exclusion Criteria: 1. Known chromosomal anomalies. 2. Newborns without central lines (e.g., lines not needed or unable to be successfully placed) or without a peripheral arterial line. 3. Patients with known cyanotic congenital heart defects 4. Patients who are participating in another clinical trial. 5. Patients who received DEX prior to enrollment in the study 6. At the discretion of the Investigator, subjects in whom the risk of Dexmedetomidine treatment is expected to exceed its benefits.

Locations (1)

Seattle Children's Hospital

Seattle, Washington, United States

Outcomes

Primary Outcomes

Pharmacokinetic (PK) parameter of area under the curve (AUC)

Estimate PK parameter of AUC in newborns ≥36 weeks post-menstrual age with hypoxic-ischemic encephalopathy treated with a continuous dexmedetomidine infusion during therapeutic hypothermia.

Time frame: Day 1 to Day 4

Pharmacokinetic (PK) parameter of clearance

Estimate PK parameter of clearance in newborns ≥36 weeks post-menstrual age with hypoxic-ischemic encephalopathy treated with a continuous dexmedetomidine infusion during therapeutic hypothermia.

Time frame: Day 1 to Day 4

Pharmacokinetic (PK) parameter of terminal half-life

Estimate PK parameter of terminal half-life in newborns ≥36 weeks post-menstrual age with hypoxic-ischemic encephalopathy treated with a continuous dexmedetomidine infusion during therapeutic hypothermia.

Time frame: Day 1 to Day 4

Pharmacokinetic (PK) of volume of distribution

Estimate PK parameter of volume of distribution in newborns ≥36 weeks post-menstrual age with hypoxic-ischemic encephalopathy treated with a continuous dexmedetomidine infusion during therapeutic hypothermia.

Time frame: Day 1 to Day 4

Secondary Outcomes

Efficacy of dexmedetomidine at preventing shivering

Measure number of morphine doses given for shivering in neonates receiving a continuous dexmedetomidine infusion during therapeutic hypothermia for hypoxic-ischemic encephalopathy.

Time frame: Day 1 to Day 3

Safety of dexmedetomidine in neonatal subjects. (composite outcome will include: adverse events, physical examination findings, and vital signs)

Safety assessments will include: adverse events, physical examination findings, vital signs including continuous heart rate, blood pressure, respiratory rate, and pulse oximetry monitoring in neonates receiving a continuous dexmedetomidine infusion during therapeutic hypothermia for hypoxic-ischemic encephalopathy.

Data from ClinicalTrials.gov

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