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

NCT04772222 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 136561
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 5

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.

Conditions

Hypoxic-Ischemic Encephalopathy; Pain

Keywords

Therapeutic hypothermia; dexmedetomidine

Outcome Measures

Primary Outcomes (1)

• Examine Safety Measures in Infants Receiving DMT to Those Receiving Morphine

  Safety will be evaluated during the first 4 days of life by comparing number of serious adverse events between two study arms.

  First 96 hours of life

Secondary Outcomes (1)

• DMT Plasma Levels

  one week

Other Outcomes (9)

• Number of Participants Who Experience Shivering

  First 96 hours of life

• Number of Days Intubated

  First week of life

• Days to Full Oral Feedings by Bottle or Breast

  Up to two months

Study Arms (2)

Dexmedetomidine (DMT)

EXPERIMENTAL

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.

Drug: Dexmedetomidine Hydrochloride

Morphine

ACTIVE COMPARATOR

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.

Drug: Morphine Sulfate

Interventions

Dexmedetomidine Hydrochloride DRUG

Potent α2-adrenergic receptor agonist that provides sedation, analgesia, and prevents shivering but does not suppress ventilation.

Dexmedetomidine (DMT)

Morphine Sulfate DRUG

Opioid agonist that provides analgesia, pain management and sedation and may suppress ventilation.

Morphine

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Known chromosomal anomalies
• Cyanotic congenital heart defects
• Redirection of care being considered because of moribund condition, or a decision made to withhold full support

Sponsors & Collaborators

• University of Utah: lead

Study Sites (5)

Intermountain Medical Center

Murray, Utah, 84107, United States

Location

McKay-Dee Hospital

Ogden, Utah, 84403, United States

Location

Utah Valley Hospital

Provo, Utah, 84604, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

University of Utah Health

Salt Lake City, Utah, 84132, United States

Location

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Pain

Interventions

Dexmedetomidine; Morphine

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

A limitation of the DICE trial design was that it was unblinded. This was due to morphine given as an intermittent bolus dose in our NICUs whereas dexmedetomidine can only be given continuous. Another important limitation was the number of protocol deviations, mostly related to N-PASS scores measured at the wrong times or drug dose adjustments not documented. This issue was as frequent in both arms of the trial but could have affected some of the results.

Results Point of Contact

• Title: Mariana Baserga, PI
• Organization: University of Utah

mariana.baserga@hsc.utah.edu

310-401-5643

Study Officials

• Mariana Baserga, MD

  University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Infants randomized to receive open-label dexmedetomidine (DMT) or morphine for pain and sedation.

Study Record Dates

• First Submitted: February 18, 2021
• First Posted: February 26, 2021
• Study Start: June 20, 2022
• Primary Completion: January 17, 2025
• Study Completion: December 31, 2025
• Last Updated: March 6, 2026
• Results First Posted: March 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)