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

University of Utah50 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hypoxic-Ischemic Encephalopathy Pain

Dexmedetomidine HydrochlorideDRUG

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

Morphine SulfateDRUG

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

Eligibility

Sex: ALLMax age: 24 Hours

Medical Language ↔ Plain English

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

Locations (5)

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, United States

Outcomes

Primary Outcomes

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.

Time frame: First 96 hours of life

Secondary Outcomes

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. Because these PK samples are done opportunistically, there are no pre-set defined time points for PK measurements.

Time frame: one week