Dexmedetomidine Versus Morphine During Cooling Therapy in Neonates

Phase 2

Not yet recruiting

• Conditions: Hypoxic Ischemic Brain Injury; Neonatal Encephalopathy; Perinatal Anoxic-ischemic Brain Injury
• Interventions: Drug: Dexmedetomidine Infusion; Drug: Morphine Infusion

• Registration Number: NCT06985290
• Lead Sponsor: Ipsita Goswami

Brief Summary

About \~3/ 1000 live-born newborns may suffer from brain injury due to a transient drop in oxygen supply to the brain during the birth process. The degree of brain injury that ensues in the first 72 hours after the injury is directly proportional to the severity of long-term childhood disabilities (e.g., cerebral palsy and developmental delays). Whole-body cooling during the first 3 days of life is proven effective in reducing the severity of brain injury. However, cooling therapy leads to pain, shivering, stress, and discomfort. The best way to alleviate the pain and agitation of cooled newborns is unknown. Standard practice is to provide morphine infusion to reduce pain. Recently, a new drug called "dexmedetomidine" has been tested in small studies and has been found to be safe during cooling in newborns. Dexmedetomidine has added beneficial effects such as anti-inflammation, faster recovery, and shorter hospital stays. This study is going to test the feasibility of conducting a future clinical trial to compare the effects of using Dexmedetomidine versus morphine in the management of cooling-related pain/agitation on the severity of brain injury in the first week of life. The study will also examine the effect of dexmedetomidine compared to morphine on short-term clinical outcomes, parental experiences and developmental outcomes at 1 year.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-27
• Status Verified: 2025-05
• Study First Submitted QC: 2025-05-14
• Last Update Submitted: 2025-05-14
• Study First Posted: 2025-05-22
• Last Update Posted: 2025-05-22
• Study Start: 2025-07-01
• Primary Completion: 2027-09-30
• Study Completion: 2028-06-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dexmedetomidine Group	Dexmedetomidine Infusion	Dexmedetomidine infusion as sedation during therapeutic hypothermia and rewarming
Morphine Group	Morphine Infusion	Morphine infusion as sedative during therapeutic hypothermia and rewarming

Primary Outcome Measures

Name	Time	Method
Recruitment Rate	Day 1	Proportion of eligible neonates enrolled. Calculation = (Number of neonates enrolled) X 100/(Total eligible neonates)
Follow Up Rate	From enrollment to 1 year of age	Percentage of neonates completing the study. Calculation = (Neonates who completed the study) x 100/ (Total neonates consented)
Adverse Event Rate	From enrollment to 7 days of life	Incidence of adverse events Measurement of Adverse Event Rate = (Number of neonates experiencing) x100/ (Total neonates exposed to the intervention)
Discontinuation Rate	From enrollment to 7 days of life	Need for intervention discontinuation due to adverse effects. Measurement of Discontinuation Rate = (Number of neonates for whom the intervention discontinued) x 100/ (Total neonates consented)
Protocol Adherence Rate	through study completion, average 1 year	Percentage of correct drug adjustment based on changes in COMFORTneo scale as per protocol. Calculation of Drug Administration Compliance = (Number of correctly administered medication per month) x 100/ (Total number of participant enrolled per month)

Secondary Outcome Measures

Name	Time	Method
Severity of Brain Injury on Magnetic Resonance Imaging (MRI)	From enrollment to 10 days of life	The T1 and T2 weighted images, diffusion-weighted images, and magnetic resonance spectroscopy (MRS) are additionally evaluated to determine the level of brain damage. MRI scoring system reported by Weeke et al. will be used to classify brain injury based on 4 subscores, including grey matter (basal ganglia, thalamus, PLIC, brainstem, perirolandic cortex, and hippocampus), white matter/cortex (including optic radiation and corpus callosum), and cerebellum.
Seizure Burden during Therapeutic Hypothermia	From enrollment to 72 hours of life	Total duration of seizures noted during the first 72 hours of life
Stress levels measured by Salivary cortisol assay at 24 and 48 hours	From enrollment to 48 hours of life	Salivary cortisol levels will be used as an objective marker of neonatal stress measured in µg/dL.
Neonatal Sedation and Discomfort Levels	From enrollment to 4 days of life	COMFORT neo scores during the period of therapeutic hypothermia. It consists of 7 behavioural items (alertness, calmness/agitation, respiratory response, crying, body movement, facial tension and muscle tone), of which six items should be scored (respiratory response or crying depends on the presence of invasive ventilation). The neonate will be observed for 2 minutes to score. Total scores range from 7 to 35. A score \>14 is considered a sign of distress and undersedation. A score \< 9 suggests oversedation.
Time to Reach Full Oral Feeds	up to 4 weeks of life	Days of life when participant is receiving all oral feeds either breast or bottle
Cumulative dose of PRN opioid boluses given during therapeutic hypothermia	up to 4 days of life	Total dose of morphine and fentanyl given during therapeutic hypothermia measured in mg/kg of morphine equivalent
Length of Hospital Stay	up to 4 weeks of life	Day of life when discharged home
Days on invasive and non-invasive respiratory support	Up to 4 weeks of life	Day of life when comes off all respiratory support to room air

Trial Locations

Locations (1)

McMaster Children's Hospital; 🇨🇦 Hamilton, Ontario, Canada