Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial)

Pain Clinical Trial

— DICE  

Official title:

Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04772222
• Other study ID #: 136561
• Status: Recruiting
• Phase: Phase 2
• Start date: June 20, 2022
• Est. completion date: August 30, 2025

Study information

• Verified date: May 2024
• Source: University of Utah
• Contact: Mariana Baserga, MD
• Phone: 801-581-4178
• Email: mariana.baserga[@]hsc.utah.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: August 30, 2025
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy
• Pain

Intervention

Drug:
• Dexmedetomidine Hydrochloride
Potent a2-adrenergic receptor agonist that provides sedation, analgesia, and prevents shivering but does not suppress ventilation.
• Morphine Sulfate
Opioid agonist that provides analgesia, pain management and sedation and may suppress ventilation.

Locations

Country	Name	City	State
United States	Intermountain Medical Center	Murray	Utah
United States	McKay-Dee Hospital	Ogden	Utah
United States	Utah Valley Hospital	Provo	Utah
United States	Primary Children's Hospital	Salt Lake City	Utah
United States	University of Utah Health	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
University of Utah

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants who experience shivering	Number of babies who experience shivering during therapeutic hypothermia will be compared between the two drug treatment regimens	First 96 hours of life
Other	Number of participants who require respiratory support	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	First week of life
Other	Days to full oral feedings by bottle or breast	Days to full oral feedings will be compared between the two drug treatment regimens	Up to two months
Other	Generalized Motor Assessment Scores (GMA) 7 days after weaned off of study drug or discharge, whichever happens first	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.	up to 3 weeks
Other	Generalized Motor Assessment Scores at 3-4 months of age	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.	3-4 months of age
Other	Hammersmith Infant Neurological Exam (HINE) scores at 3-4 months of age	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.	3-4 months of age
Other	Hammersmith Infant Neurological Exam (HINE) scores at 6-9 months of age	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.	6-9 months of age
Other	Test of Infant Motor Performance (TIMP) scores at 3-4 months of corrected age	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.	3-4 months of corrected age
Other	Peabody Developmental Motor Skills (PDMS-2) at 6-9 months of age	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.	6-9 months of age
Other	Ages and Stages Questionnaire at 6-9 months of age	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	6-9 months of age
Primary	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.	First 96 hours of life
Secondary	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.	one week