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Dexmedetomidine Pharmacokinetics in Neonates During Therapeutic Hypothermia

Primary Purpose

Hypoxic-ischemic Encephalopathy

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dexmedetomidine
Sponsored by
Seattle Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypoxic-ischemic Encephalopathy focused on measuring 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

Eligibility Criteria

1 Hour - 1 Day (Child)All SexesDoes not accept 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.

Sites / Locations

  • Seattle Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dexmedetomidine group

Arm 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).

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

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.
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.

Full Information

First Posted
August 6, 2015
Last Updated
January 10, 2017
Sponsor
Seattle Children's Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02529202
Brief Title
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

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
January 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seattle Children's Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
7 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dexmedetomidine group
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine
Other Intervention Name(s)
Precedex
Intervention Description
Dexmedetomidine infusion
Primary Outcome Measure Information:
Title
Pharmacokinetic (PK) parameter of area under the curve (AUC)
Description
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
Title
Pharmacokinetic (PK) parameter of clearance
Description
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
Title
Pharmacokinetic (PK) parameter of terminal half-life
Description
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
Title
Pharmacokinetic (PK) of volume of distribution
Description
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 Outcome Measure Information:
Title
Efficacy of dexmedetomidine at preventing shivering
Description
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
Title
Safety of dexmedetomidine in neonatal subjects. (composite outcome will include: adverse events, physical examination findings, and vital signs)
Description
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.
Time Frame
Day 1 to Day 4

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Hour
Maximum Age & Unit of Time
1 Day
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Cooled infants who are initially intubated and mechanically ventilated. Infants anticipated to require 72 hrs of continuous sedation and/or treatment to prevent shivering. 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: Known chromosomal anomalies. Newborns without central lines (e.g., lines not needed or unable to be successfully placed) or without a peripheral arterial line. Patients with known cyanotic congenital heart defects Patients who are participating in another clinical trial. Patients who received DEX prior to enrollment in the study At the discretion of the Investigator, subjects in whom the risk of Dexmedetomidine treatment is expected to exceed its benefits.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan M McAdams, MD
Organizational Affiliation
Seattle Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98015
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Dexmedetomidine Pharmacokinetics in Neonates During Therapeutic Hypothermia

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