Clinical trial NCT02529202: Dexmedetomidine Pharmacokinetics in Neonates During Therapeutic Hypothermia
Official title: Dexmedetomidine Use During Therapeutic Hypothermia Treatment for Neonates With Hypoxic-ischemic Encephalopathy: The Cool DEX Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hypoxic-ischemic Encephalopathy
Keywords: Dexmedetomidine
Neonate
Pharmacokinetics
Therapeutic Hypothermia
Hypoxic-ischemic Encephalopathy
Adrenergic Agents
Adrenergic Agonists
Analgesics
Adrenergic alpha-2 Receptor Agonists
Central Nervous System Agents
Central Nervous System Depressants
Lead sponsor: Seattle Children's Hospital
Sponsor class: OTHER
First posted: 2015-08-20
Enrollment: 7
Sex: ALL
Minimum age (years): 1
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Pharmacokinetic (PK) parameter of area under the curve (AUC)
timeFrame: Day 1 to Day 4
measure: Pharmacokinetic (PK) parameter of clearance
timeFrame: Day 1 to Day 4
measure: Pharmacokinetic (PK) parameter of terminal half-life
timeFrame: Day 1 to Day 4
measure: Pharmacokinetic (PK) of volume of distribution
timeFrame: Day 1 to Day 4
Secondary outcomes:
measure: Efficacy of dexmedetomidine at preventing shivering
timeFrame: Day 1 to Day 3
measure: Safety of dexmedetomidine in neonatal subjects. (composite outcome will include: adverse events, physical examination findings, and vital signs)
timeFrame: Day 1 to Day 4
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Seattle Children's Hospital
name: Ryan M McAdams, MD
role: PRINCIPAL_INVESTIGATOR
References: