Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial) (DICE)
Primary Purpose
Hypoxic-Ischemic Encephalopathy, Pain
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Dexmedetomidine Hydrochloride
Morphine Sulfate
Sponsored by
About this trial
This is an interventional treatment trial for Hypoxic-Ischemic Encephalopathy focused on measuring Therapeutic hypothermia, dexmedetomidine
Eligibility Criteria
Inclusion Criteria:
- Neonates ≥36 weeks' gestational age diagnosed with moderate-to-severe neonatal encephalopathy and treated with TH (target temperature 33.5°C) for a planned duration of 72 h.
- Infants requiring sedation and/or treatment to prevent shivering during TH as assessed by the Neonatal Pain, Agitation, and Sedation Scale (N-PASS) scores and a modified Bedside Shivering Assessment Scale.
- Informed consent document approved by the Institutional Review Board (IRB) obtained prior to randomization
Exclusion Criteria:
- Known chromosomal anomalies
- Cyanotic congenital heart defects
- Redirection of care being considered because of moribund condition, or a decision made to withhold full support
Sites / Locations
- Intermountain Medical CenterRecruiting
- McKay-Dee HospitalRecruiting
- Utah Valley HospitalRecruiting
- Primary Children's HospitalRecruiting
- University of Utah HealthRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Dexmedetomidine (DMT)
Morphine
Arm Description
Subjects randomized to DMT arm in a 1:1 ratio. A loading dose of 1 mcg/kg will be given followed by 0.1 to 0.5 mcg/kg/h continuous infusion. The Neonatal Pain, Agitation, and Sedation Scale (N-PASS) will be used to determine infusion rate.
Subjects randomized to morphine in a 1:1 ratio. Intermittent dosing every 3-4 hours of 0.02-0.05 mg/kg/dose or continuous infusion of 0.005 to 0.01 mg/kg/hr. The N-PASS will be used to determine dosing and frequency.
Outcomes
Primary Outcome Measures
Examine Safety Measures in infants receiving DMT to those receiving morphine
Safety will be evaluated during the first 4 days of life by documenting potential adverse events such hypotension, hypertension, bradycardia, cardiac arrhythmias, hypothermia, acute renal failure, liver failure, and seizures outside of normal range for the study population.
Secondary Outcome Measures
DMT plasma levels
Two opportunistic PK samples (at time of routine laboratories) and a PK sample any time there is an adverse event will be obtained for measurement of DMT plasma concentrations as needed.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04772222
Brief Title
Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial)
Acronym
DICE
Official Title
Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 20, 2022 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Utah
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Management of neonatal pain and sedation often includes opioid therapy. A growing body of evidence suggests long-term harm associated with neonatal opioid exposure. Providing optimal sedation while neonates are undergoing therapeutic hypothermia (TH) may be beneficial but also presents therapeutic challenges. While there is evidence from animal models of brain injury and clinical trials in adults to support the safety and neuroprotective properties of dexmedetomidine (DMT), there are no published large clinical trials demonstrating safety and efficacy of DMT use in neonates with hypoxic-ischemic encephalopathy (HIE) during treatment with TH. This study is innovative in proposing a Phase II, 2-arm trial providing the opportunity to evaluate the use of DMT as compared to the use of morphine for sedation and pain management for babies undergoing TH. We propose to confirm optimal DMT dosing by collecting opportunistic pharmacokinetics (PK) data and determine safety of DMT in this population. These data will inform a larger phase III efficacy trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxic-Ischemic Encephalopathy, Pain
Keywords
Therapeutic hypothermia, dexmedetomidine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Infants randomized to receive open-label dexmedetomidine (DMT) or morphine for pain and sedation.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Dexmedetomidine (DMT)
Arm Type
Experimental
Arm Description
Subjects randomized to DMT arm in a 1:1 ratio. A loading dose of 1 mcg/kg will be given followed by 0.1 to 0.5 mcg/kg/h continuous infusion. The Neonatal Pain, Agitation, and Sedation Scale (N-PASS) will be used to determine infusion rate.
Arm Title
Morphine
Arm Type
Active Comparator
Arm Description
Subjects randomized to morphine in a 1:1 ratio. Intermittent dosing every 3-4 hours of 0.02-0.05 mg/kg/dose or continuous infusion of 0.005 to 0.01 mg/kg/hr. The N-PASS will be used to determine dosing and frequency.
Intervention Type
Drug
Intervention Name(s)
Dexmedetomidine Hydrochloride
Intervention Description
Potent α2-adrenergic receptor agonist that provides sedation, analgesia, and prevents shivering but does not suppress ventilation.
Intervention Type
Drug
Intervention Name(s)
Morphine Sulfate
Intervention Description
Opioid agonist that provides analgesia, pain management and sedation and may suppress ventilation.
Primary Outcome Measure Information:
Title
Examine Safety Measures in infants receiving DMT to those receiving morphine
Description
Safety will be evaluated during the first 4 days of life by documenting potential adverse events such hypotension, hypertension, bradycardia, cardiac arrhythmias, hypothermia, acute renal failure, liver failure, and seizures outside of normal range for the study population.
Time Frame
First 96 hours of life
Secondary Outcome Measure Information:
Title
DMT plasma levels
Description
Two opportunistic PK samples (at time of routine laboratories) and a PK sample any time there is an adverse event will be obtained for measurement of DMT plasma concentrations as needed.
Time Frame
one week
Other Pre-specified Outcome Measures:
Title
Number of participants who experience shivering
Description
Number of babies who experience shivering during therapeutic hypothermia will be compared between the two drug treatment regimens
Time Frame
First 96 hours of life
Title
Number of participants who require respiratory support
Description
Number of babies who require respiratory support will be compared between the two drug treatment regimens. This will include ventilator, continuous positive airway pressure, and oxygen use
Time Frame
First week of life
Title
Days to full oral feedings by bottle or breast
Description
Days to full oral feedings will be compared between the two drug treatment regimens
Time Frame
Up to two months
Title
Generalized Motor Assessment Scores (GMA) 7 days after weaned off of study drug or discharge, whichever happens first
Description
the GMA is a validated test that aids in early detection of neurological movement disorders by evaluating the quality of movements during a 2-minute video. Certified assessors will grade the quality of movements which include: normal writhing, poor repertoire, cramped synchronized, and chaotic movements. All movements other than normal writhing are considered atypical. The results will be compared between the two drug treatments.
Time Frame
up to 3 weeks
Title
Generalized Motor Assessment Scores at 3-4 months of age
Description
the GMA is a validated test that aids in early detection of neurological movement disorders by evaluating the quality of movements during a 2-minute video. Certified assessors will grade the quality of movements which include: normal writhing, poor repertoire, cramped synchronized, and chaotic movements. All movements other than normal writhing are considered atypical. The results will be compared between the two drug treatments.
Time Frame
3-4 months of age
Title
Hammersmith Infant Neurological Exam (HINE) scores at 3-4 months of age
Description
The HINE is a 26 item exam that assesses different aspects of neurological function and these scores will be compared between the two drug treatment regimens. This assessment scores 5 different neurological development areas: Cranial nerve function, posture, movements, tone, and reflexes/reactions. The maximum score is 78 and lowest score is 0. Higher scores show better neurological development consistent with better outcomes.
Time Frame
3-4 months of age
Title
Hammersmith Infant Neurological Exam (HINE) scores at 6-9 months of age
Description
The HINE is a 26 item exam that assesses different aspects of neurological function and these scores will be compared between the two drug treatment regimens. This assessment scores 5 different neurological development areas: Cranial nerve function, posture, movements, tone, and reflexes/reactions. The maximum score is 78 and lowest score is 0. Higher scores show better neurological development consistent with better outcomes.
Time Frame
6-9 months of age
Title
Test of Infant Motor Performance (TIMP) scores at 3-4 months of corrected age
Description
This test evaluates posture and motor control and is designed to be used specifically in infants born prematurely. Results are given based on z-scores from normative values and are given as low average, below average, and far below average. Lower scores are more predictive of worse outcomes. These scores will be compared between the two drug treatment regimens.
Time Frame
3-4 months of corrected age
Title
Peabody Developmental Motor Skills (PDMS-2) at 6-9 months of age
Description
This test evaluates fine motor, gross motor, and total motor skills. Results are converted to age equivalent rating and then quotient scores are given for each category. Minimum is 35 and maximum is 165. The average score is 90-110, with higher scores given in 3 SD above average performance and lower scores given in 3 SD below average performance.The higher the score, the better predicted outcome. These scores will be compared between the two drug treatment regimens.
Time Frame
6-9 months of age
Title
Ages and Stages Questionnaire at 6-9 months of age
Description
Parental survey that assesses communication, gross and fine motor skills, and social behaviors. Scores range from 0-60, and the higher the score, the better the outcome.
These scores will be compared between the two drug treatment regimens
Time Frame
6-9 months of age
10. Eligibility
Sex
All
Maximum Age & Unit of Time
24 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Neonates ≥36 weeks' gestational age diagnosed with moderate-to-severe neonatal encephalopathy and treated with TH (target temperature 33.5°C) for a planned duration of 72 h.
Infants requiring sedation and/or treatment to prevent shivering during TH as assessed by the Neonatal Pain, Agitation, and Sedation Scale (N-PASS) scores and a modified Bedside Shivering Assessment Scale.
Informed consent document approved by the Institutional Review Board (IRB) obtained prior to randomization
Exclusion Criteria:
Known chromosomal anomalies
Cyanotic congenital heart defects
Redirection of care being considered because of moribund condition, or a decision made to withhold full support
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mariana Baserga, MD
Phone
801-581-4178
Email
mariana.baserga@hsc.utah.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Carrie Rau, RN
Phone
801-213-3360
Email
carrie.rau@hsc.utah.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mariana Baserga, MD
Organizational Affiliation
University of Utah
Official's Role
Principal Investigator
Facility Information:
Facility Name
Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Baserga, MD
Phone
801-581-4178
Email
Mariana.Baserga@hsc.utah.edu
First Name & Middle Initial & Last Name & Degree
Kimberlee Weaver-Lewis, RN, MS
Phone
801-507-7675
Email
kimberlee.weaverlewis@imail.org
Facility Name
McKay-Dee Hospital
City
Ogden
State/Province
Utah
ZIP/Postal Code
84403
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Baserga, MD
Phone
801-581-4178
Email
mariana.baserga@hsc.utah.edu
First Name & Middle Initial & Last Name & Degree
Kimberlee Weaver-Lewis, RN, MS
Phone
801-507-7675
Email
kimberlee.weaverlewis@imail.org
Facility Name
Utah Valley Hospital
City
Provo
State/Province
Utah
ZIP/Postal Code
84604
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Baserga, MD
Phone
801-581-4178
Email
mariana.baserga@hsc.utah.edu
First Name & Middle Initial & Last Name & Degree
Kimberlee Weaver-Lewis, RN, MS
Phone
801-507-7675
Email
kimberlee.weaverlewis@imail.org
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84113
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Baserga, MD
Phone
801-581-4178
Email
Mariana.Baserga@hsc.utah.edu
First Name & Middle Initial & Last Name & Degree
Kimberlee Weaver-Lewis, RN
Phone
801-507-7675
Email
kimberlee.weaverlewis@imail.org
Facility Name
University of Utah Health
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariana Baserga, MD
Phone
801-581-4178
Email
mariana.baserga@hsc.utah.edu
First Name & Middle Initial & Last Name & Degree
Carrie Rau, RN
Phone
801-213-3360
Email
carrie.rau@hsc.utah.edu
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial)
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