Dexmedetomidine Pharmacokinetics in Neonates During Therapeutic Hypothermia

Seattle Children's Healthcare System

Status and phase: Completed; Early Phase 1

Conditions: Hypoxic-ischemic Encephalopathy

Treatments: Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other

Identifiers

NCT02529202

15647

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 7 patients

Sex: All

Ages: 1 hour to 1 day old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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7 participants in 1 patient group

Dexmedetomidine group

Experimental group

Description:

Neonates with hypoxic-ischemic encephalopathy will receive a dexmedetomidine maintenance infusion of 0.4 mcg/kg/hr during treatment with therapeutic hypothermia and during re-warming (78 hours total).

Treatment:

Drug: Dexmedetomidine