Dexmedetomidine Versus Morphine During Cooling Therapy in Neonates

NCT06985290 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: 20027280
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxic Ischemic Brain Injury; Neonatal Encephalopathy; Perinatal Anoxic-ischemic Brain Injury

Keywords

sedation; analgesia; dexmedetomidine; morphine

Outcome Measures

Primary Outcomes (5)

• Recruitment Rate

  Proportion of eligible neonates enrolled. Calculation = (Number of neonates enrolled) X 100/(Total eligible neonates)

  Day 1

• Follow Up Rate

  Percentage of neonates completing the study. Calculation = (Neonates who completed the study) x 100/ (Total neonates consented)

  From enrollment to 1 year of age

• Adverse Event Rate

  Incidence of adverse events Measurement of Adverse Event Rate = (Number of neonates experiencing) x100/ (Total neonates exposed to the intervention)

  From enrollment to 7 days of life

• Discontinuation Rate

  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)

  From enrollment to 7 days of life

• Protocol Adherence Rate

  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)

  through study completion, average 1 year

Secondary Outcomes (8)

• Severity of Brain Injury on Magnetic Resonance Imaging (MRI)

  From enrollment to 10 days of life

• Seizure Burden during Therapeutic Hypothermia

  From enrollment to 72 hours of life

• Stress levels measured by Salivary cortisol assay at 24 and 48 hours

  From enrollment to 48 hours of life

• Neonatal Sedation and Discomfort Levels

  From enrollment to 4 days of life

• Time to Reach Full Oral Feeds

  up to 4 weeks of life

Other Outcomes (3)

• Parental Stress Index

  Up to 4 weeks of life

• Parental Experiences

  From discharge to 4 weeks post-discharge

• Developmental Outcomes at 12 months

  Between 10-14 months of enrollment

Study Arms (2)

Dexmedetomidine Group

EXPERIMENTAL

Dexmedetomidine infusion as sedation during therapeutic hypothermia and rewarming

Drug: Dexmedetomidine Infusion

Morphine Group

ACTIVE COMPARATOR

Morphine infusion as sedative during therapeutic hypothermia and rewarming

Drug: Morphine Infusion

Interventions

Dexmedetomidine Infusion DRUG

Dexmedetomidine infusion given for sedation during therapeutic hypothermia. Dexmedetomidine infusion at a starting dose of 0.2 μg/kg/h, with titration in 0.1 μg/kg/h increments with a maximum of 0.5 μg/kg/h based on objective assessment of sedation.

Dexmedetomidine Group

Morphine Infusion DRUG

Morphine infusion given for sedation during therapeutic hypothermia. Morphine infusion at a starting dose of 4 μg/kg/h, with titration in 2 μg/kg/h increments with a maximum of 10 μg/kg/h based on objective assessment of sedation.

Morphine Group

Eligibility Criteria

• Age: Up to 20 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age \>= 35 weeks
• Birth weight \>= 2500g
• Sign of perinatal hypoxic event (any of the following): (a) Arterial Cord blood gas or postnatal gas within 1 hour of life pH \<= 7.00 OR Base Deficit \>= 16 (b) Arterial Cord blood gas postnatal gas within 1 hour of life pH 7.00 -7.15 AND Acute sentinel intrapartum event
• Sign of Neonatal Encephalopathy
• Initiation of Therapeutic Hypothermia within 8 hours of life

You may not qualify if:

• Informed consent not obtained within 20 hours of life
• Congenital Brain Malformations (antenatally known)
• Major Chromosomal Anomaly (antenatally diagnosed)
• Congenital neuromuscular disorder

Sponsors & Collaborators

• Ipsita Goswami: lead

Study Sites (1)

McMaster Children's Hospital

Hamilton, Ontario, L8N3Z5, Canada

Location

Related Publications (19)

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• Thoresen M, Satas S, Loberg EM, Whitelaw A, Acolet D, Lindgren C, Penrice J, Robertson N, Haug E, Steen PA. Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective. Pediatr Res. 2001 Sep;50(3):405-11. doi: 10.1203/00006450-200109000-00017.

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MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Agnosia

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; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations

Study Officials

• Ipsita Goswami, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

IPSITA GOSWAMI, MD

CONTACT

9055212100; goswamii@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 27, 2025
• First Posted: May 22, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: May 22, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be available beginning 12 months after publication of the primary results or within 18 months of primary study completion, whichever occurs first. Data will be available for at least 5 years thereafter.
• Access Criteria: Researchers must submit a scientifically sound proposal. Access will be granted upon approval by the Data Access Committee and signing of a Data Use Agreement (DUA). Data must be used for secondary analyses, meta-analyses, or validation studies. Re-identification attempts are prohibited.

Locations

CA (1)