Dexmedetomidine Pharmacokinetics in Neonates During Therapeutic Hypothermia

January 10, 2017 updated by: Ryan McAdams, Seattle Children's Hospital

Dexmedetomidine Use During Therapeutic Hypothermia Treatment for Neonates With Hypoxic-ischemic Encephalopathy: The Cool DEX Study

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
7

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98015
        • Seattle Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 hour to 1 day (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dexmedetomidine group
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).
Drug: Dexmedetomidine
Dexmedetomidine infusion
Other Names:
  • Precedex

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetic (PK) parameter of area under the curve (AUC)
Time Frame: Day 1 to Day 4
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.
Day 1 to Day 4
Pharmacokinetic (PK) parameter of clearance
Time Frame: Day 1 to Day 4
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.
Day 1 to Day 4
Pharmacokinetic (PK) parameter of terminal half-life
Time Frame: Day 1 to Day 4
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.
Day 1 to Day 4
Pharmacokinetic (PK) of volume of distribution
Time Frame: Day 1 to Day 4
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.
Day 1 to Day 4

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Efficacy of dexmedetomidine at preventing shivering
Time Frame: Day 1 to Day 3
Measure number of morphine doses given for shivering in neonates receiving a continuous dexmedetomidine infusion during therapeutic hypothermia for hypoxic-ischemic encephalopathy.
Day 1 to Day 3
Safety of dexmedetomidine in neonatal subjects. (composite outcome will include: adverse events, physical examination findings, and vital signs)
Time Frame: Day 1 to Day 4
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.
Day 1 to Day 4

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Seattle Children's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ryan M McAdams, MD, Seattle Children's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 6, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 18, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 20, 2015

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 12, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 10, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15647

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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