Hypoxic-Ischemic Encephalopathy, Pain
Conditions
Keywords
Therapeutic hypothermia, dexmedetomidine
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.
Interventions
DRUGDexmedetomidine Hydrochloride
Potent α2-adrenergic receptor agonist that provides sedation, analgesia, and prevents shivering but does not suppress ventilation.
DRUGMorphine Sulfate
Opioid agonist that provides analgesia, pain management and sedation and may suppress ventilation.
Sponsors
University of Utah
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Infants randomized to receive open-label dexmedetomidine (DMT) or morphine for pain and sedation.
Eligibility
Sex/Gender
ALL
Age
No minimum to 24 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Examine Safety Measures in Infants Receiving DMT to Those Receiving Morphine | First 96 hours of life | Safety will be evaluated during the first 4 days of life by comparing number of serious adverse events between two study arms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| DMT Plasma Levels | one week | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMariana Baserga, MD
University of Utah
Participant flow
Recruitment details
Enrolled from June 2022 to Jan 2025 and a total of 50 babies were consented to the study. Two babies were withdrawn due to no receipt of study drug, making enrollment of evaluable babies a total of 48.Due to slow enrollment and lack of funding, enrollment of evaluable babies completed at 48 instead of 50.
Pre-assignment details
The intent of the protocol was to replace any babies who were deemed not evaluable (didn't receive study drug) with another enrollment to have a total of 50 evaluable subjects enrolled.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 48 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 48 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 1 / 23 |
| other Total, other adverse events | 16 / 25 | 8 / 23 |
| serious Total, serious adverse events | 1 / 25 | 1 / 23 |
Outcome results
None listed