Trial Outcomes & Findings for Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial) (NCT NCT04772222)
NCT ID: NCT04772222
Last Updated: 2026-03-06
Results Overview
Safety will be evaluated during the first 4 days of life by comparing number of serious adverse events between two study arms.
COMPLETED
PHASE2
50 participants
First 96 hours of life
2026-03-06
Participant Flow
Enrolled from June 2022 to Jan 2025 and a total of 50 babies were consented to the study. Two babies were withdrawn due to no receipt of study drug, making enrollment of evaluable babies a total of 48.Due to slow enrollment and lack of funding, enrollment of evaluable babies completed at 48 instead of 50.
The intent of the protocol was to replace any babies who were deemed not evaluable (didn't receive study drug) with another enrollment to have a total of 50 evaluable subjects enrolled.
Participant milestones
| Measure |
Dexmedetomidine (DMT)
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.
Dexmedetomidine Hydrochloride: Potent α2-adrenergic receptor agonist that provides sedation, analgesia, and prevents shivering but does not suppress ventilation.
|
Morphine
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.
Morphine Sulfate: Opioid agonist that provides analgesia, pain management and sedation and may suppress ventilation.
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
24
|
|
Overall Study
COMPLETED
|
25
|
23
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
Reasons for withdrawal
| Measure |
Dexmedetomidine (DMT)
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.
Dexmedetomidine Hydrochloride: Potent α2-adrenergic receptor agonist that provides sedation, analgesia, and prevents shivering but does not suppress ventilation.
|
Morphine
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.
Morphine Sulfate: Opioid agonist that provides analgesia, pain management and sedation and may suppress ventilation.
|
|---|---|---|
|
Overall Study
Did not receive study drug
|
1
|
1
|
Baseline Characteristics
Dexmedetomidine Use in Infants Undergoing Cooling Due to Neonatal Encephalopathy (DICE Trial)
Baseline characteristics by cohort
| Measure |
Dexmedetomidine (DMT)
n=25 Participants
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.
Dexmedetomidine Hydrochloride: Potent α2-adrenergic receptor agonist that provides sedation, analgesia, and prevents shivering but does not suppress ventilation.
|
Morphine
n=23 Participants
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.
Morphine Sulfate: Opioid agonist that provides analgesia, pain management and sedation and may suppress ventilation.
|
Total
n=48 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
2 Participants
n=76 Participants
|
|
Age, Categorical
<=18 years
|
25 Participants
n=41 Participants
|
23 Participants
n=35 Participants
|
48 Participants
n=76 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=76 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=76 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=41 Participants
|
11 Participants
n=35 Participants
|
21 Participants
n=76 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=41 Participants
|
12 Participants
n=35 Participants
|
27 Participants
n=76 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=41 Participants
|
9 Participants
n=35 Participants
|
15 Participants
n=76 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
18 Participants
n=41 Participants
|
14 Participants
n=35 Participants
|
32 Participants
n=76 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
1 Participants
n=76 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=76 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=41 Participants
|
1 Participants
n=35 Participants
|
2 Participants
n=76 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
2 Participants
n=76 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=41 Participants
|
18 Participants
n=35 Participants
|
33 Participants
n=76 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=41 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=76 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
5 Participants
n=41 Participants
|
4 Participants
n=35 Participants
|
9 Participants
n=76 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=41 Participants
|
23 participants
n=35 Participants
|
48 participants
n=76 Participants
|
PRIMARY outcome
Timeframe: First 96 hours of lifeSafety will be evaluated during the first 4 days of life by comparing number of serious adverse events between two study arms.
Outcome measures
| Measure |
Dexmedetomidine (DMT)
n=25 Participants
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.
|
Morphine
n=23 Participants
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.
|
|---|---|---|
|
Examine Safety Measures in Infants Receiving DMT to Those Receiving Morphine
|
1 Number of serious adverse events
|
1 Number of serious adverse events
|
SECONDARY outcome
Timeframe: one weekPopulation: Pharmacokinetics were only analyzed in the dexmedetomidine group.
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. Because these PK samples are done opportunistically, there are no pre-set defined time points for PK measurements.
Outcome measures
| Measure |
Dexmedetomidine (DMT)
n=25 Participants
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.
|
Morphine
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.
|
|---|---|---|
|
DMT Plasma Levels
|
651 Dexemedetomidine concentration in pg/mL
Interval 90.5 to 2960.0
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: First 96 hours of lifeNumber of babies who experience shivering during therapeutic hypothermia will be compared between the two drug treatment regimens
Outcome measures
| Measure |
Dexmedetomidine (DMT)
n=25 Participants
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.
|
Morphine
n=23 Participants
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.
|
|---|---|---|
|
Number of Participants Who Experience Shivering
|
13 Participants
|
14 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: First week of lifeNumber of days each subject required invasive ventilator support will be compared between arms.
Outcome measures
| Measure |
Dexmedetomidine (DMT)
n=25 Participants
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.
|
Morphine
n=23 Participants
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.
|
|---|---|---|
|
Number of Days Intubated
|
2 Number of days intubated
Interval 0.0 to 4.0
|
1 Number of days intubated
Interval 0.0 to 5.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Up to two monthsDays to full oral feedings will be compared between the two drug treatment regimens
Outcome measures
| Measure |
Dexmedetomidine (DMT)
n=25 Participants
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.
|
Morphine
n=23 Participants
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.
|
|---|---|---|
|
Days to Full Oral Feedings by Bottle or Breast
|
11 Number of days to full feeds
Interval 5.0 to 14.0
|
7 Number of days to full feeds
Interval 5.0 to 9.0
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3-4 months of agethe 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 3-4 months of ageThe 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 6-9 months of ageThe 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 3-4 months of corrected ageThis 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 6-9 months of ageThis 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 6-9 months of ageParental 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
Outcome measures
Outcome data not reported
Adverse Events
Dexmedetomidine (DMT)
Morphine
Serious adverse events
| Measure |
Dexmedetomidine (DMT)
n=25 participants at risk
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.
|
Morphine
n=23 participants at risk
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.
|
|---|---|---|
|
General disorders
Multi-organ failure
|
0.00%
0/25 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
4.3%
1/23 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
4.0%
1/25 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
0.00%
0/23 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
Other adverse events
| Measure |
Dexmedetomidine (DMT)
n=25 participants at risk
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.
|
Morphine
n=23 participants at risk
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.
|
|---|---|---|
|
Cardiac disorders
Bradycardia
|
20.0%
5/25 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
13.0%
3/23 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
|
Cardiac disorders
Tachycardia
|
8.0%
2/25 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
0.00%
0/23 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
|
Cardiac disorders
Hypotension
|
32.0%
8/25 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
13.0%
3/23 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
|
Cardiac disorders
Hypertension
|
32.0%
8/25 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
34.8%
8/23 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
|
Nervous system disorders
Seizures
|
8.0%
2/25 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
0.00%
0/23 • Adverse events were reported that occured from randomization to 96 hours of life (study interventions phase). Serious adverse events were recorded if they occurred from randomization to 7 days post last study drug dose or hospital discharge up to 11 days, whichever occurred first.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place