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

Utah System of Higher Education (USHE)

Status and phase: Active, not recruiting; Phase 2

Conditions: Pain; Hypoxic-Ischemic Encephalopathy

Treatments: Drug: Dexmedetomidine Hydrochloride; Drug: Morphine Sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT04772222

136561

Details and patient eligibility

About

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.

Enrollment: 50 estimated patients

Sex: All

Ages: Under 24 hours old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Dexmedetomidine (DMT)

Experimental group

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.

Treatment:

Drug: Dexmedetomidine Hydrochloride

Morphine

Active Comparator group

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.

Treatment:

Drug: Morphine Sulfate