Dexmedetomidine Pharmacokinetics in Neonates During Therapeutic Hypothermia

Hypoxic-ischemic Encephalopathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02529202
• Other study ID #: 15647
• Status: Completed
• Phase: Phase 0
• First received: August 6, 2015
• Last updated: January 10, 2017
• Start date: March 2016
• Est. completion date: January 2017

Study information

• Verified date: January 2017
• Source: Seattle Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: January 2017
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 1 Day

Eligibility

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 Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypothermia
• Hypoxia-Ischemia, Brain
• Hypoxic-ischemic Encephalopathy
• Ischemia

Intervention

Drug:
• Dexmedetomidine
Dexmedetomidine infusion

Locations

Country	Name	City	State
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Seattle Children's Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1 to Day 4	No
Primary	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.	Day 1 to Day 4	No
Primary	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.	Day 1 to Day 4	No
Primary	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.	Day 1 to Day 4	No
Secondary	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.	Day 1 to Day 3	No
Secondary	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.	Day 1 to Day 4	Yes