Dexmedetomidine for Neonatal Encephalopathy

(COOL-SED Trial)

Overseen By IPSITA GOSWAMI, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Ipsita Goswami

Disqualifiers: Congenital brain malformations, major chromosomal anomaly, congenital neuromuscular disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way to manage pain and agitation in newborns who have experienced a lack of oxygen at birth, which can lead to brain injury. It compares two treatments: dexmedetomidine, a newer drug with potential benefits such as reducing inflammation and shortening hospital stays, and the standard treatment, morphine. The trial will determine which drug better reduces pain and improves outcomes in the first week of life. Babies who are at least 35 weeks old at birth, weigh over 2500 grams, and show signs of oxygen deprivation are suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Do I need to stop my current medications for the trial?

The trial information does not specify whether participants need to stop taking their current medications. It is best to consult with the trial coordinators for specific guidance.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that dexmedetomidine is generally safe for newborns requiring cooling therapy. In studies, it effectively calmed infants with conditions similar to those in this trial. The most common side effects were mild, such as changes in blood pressure, and were manageable. Dexmedetomidine also offered potential benefits, including quicker recovery and shorter hospital stays.

For morphine, which is already widely used, extensive safety information is available. It effectively reduces pain in newborns but can cause side effects like breathing problems. Both treatments have been used safely, but dexmedetomidine might offer additional benefits beyond pain relief. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about dexmedetomidine for neonatal encephalopathy because it offers a unique approach to sedation during therapeutic hypothermia. Unlike traditional sedatives like morphine, dexmedetomidine works by selectively targeting alpha-2 adrenergic receptors, which can provide sedation without the respiratory depression often associated with opioids. This mechanism might result in a safer sedation profile for vulnerable newborns. Additionally, dexmedetomidine's potential to enhance neuroprotection during cooling therapy is an aspect that researchers are keen to explore, as it could lead to improved outcomes for infants with this condition.

What evidence suggests that this trial's treatments could be effective for neonatal encephalopathy?

This trial will compare dexmedetomidine and morphine for calming newborns with hypoxic-ischemic encephalopathy (HIE) during therapeutic hypothermia and rewarming. Studies have shown that dexmedetomidine can be a safe and effective choice, potentially reducing swelling and speeding recovery, which could lead to shorter hospital stays. Animal research suggests it might protect brain cells and improve outcomes after oxygen deprivation at birth. Additionally, dexmedetomidine might better manage pain and keep these newborns calm compared to morphine. While more research is needed, these early findings are promising for its use in this situation. ^{1 2 6 7 8}

Who Is on the Research Team?

Ipsita Goswami, MD

Principal Investigator

McMaster University

Are You a Good Fit for This Trial?

This trial is for newborns who have suffered brain injury due to oxygen deprivation during birth. They must be undergoing cooling therapy within the first 72 hours of life to reduce brain injury severity. Specific eligibility details are not provided, but typically include certain health parameters and parental consent.

Inclusion Criteria

My treatment with cooling therapy started within 8 hours of being born.

Gestational age >= 35 weeks

Birth weight >= 2500g

Exclusion Criteria

Congenital Brain Malformations (antenatally known)

Congenital neuromuscular disorder

My unborn baby has been diagnosed with a major chromosomal anomaly.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either Dexmedetomidine or Morphine infusion as sedation during therapeutic hypothermia and rewarming

3 days

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including developmental outcomes at 1 year

1 year

Regular follow-up visits and assessments

Extension

Parental experiences and stress levels are assessed post-discharge

4 weeks post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine
• Morphine

Trial Overview The study compares two drugs: Dexmedetomidine and Morphine, both given through an infusion to manage pain in cooled newborns with brain injuries. It aims to determine which drug better reduces pain and improves outcomes like recovery time and developmental progress at one year.

How Is the Trial Designed?

Group I: Dexmedetomidine Group Experimental Treatment 1 Intervention

Dexmedetomidine infusion as sedation during therapeutic hypothermia and rewarming

Group II: Morphine Group Active Control 1 Intervention

Morphine infusion as sedative during therapeutic hypothermia and rewarming

Who Is Running the Clinical Trial?

Ipsita Goswami

Lead Sponsor

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11163906/

Effectiveness and Safety of Dexmedetomidine in Neonates ... Dexmedetomidine as monotherapy was effective and safe sedation for infants with HIE undergoing hypothermia. The most common side effect of dexmedetomidine was ...

2. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2021.770511/epub

Dexmedetomidine Use in Neonatal HIE Results and Conclusions: Dexmedetomidine may be a better alternative to morphine for the treatment of pain and sedation in newborns with HIE ...

3. karger.com karger.com/neo/article/122/4/495/926532/Dexmedetomidine-as-a-Promising-Neuroprotective

Dexmedetomidine as a Promising Neuroprotective ... In animal studies, dexmedetomidine has been shown to enhance neuronal survival after umbilical cord occlusion and to suppress inflammatory ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06985290

Study Details | NCT06985290 | Dexmedetomidine Versus ... Dexmedetomidine has added beneficial effects such as anti-inflammation, faster recovery, and shorter hospital stays.

5. bmjpaedsopen.bmj.com bmjpaedsopen.bmj.com/content/9/1/e003004

Dexmedetomidine in neonates: utilisation trends and safety ... Conclusion Our data and experiences demonstrated a significant increase in the dose and duration of dexmedetomidine use in the NICU over the ...

6. publications.aap.org publications.aap.org/hospitalpediatrics/article/14/1/30/196237/Dexmedetomidine-During-Therapeutic-Hypothermia-A

Dexmedetomidine During Therapeutic Hypothermia One-hundred and fifty-four neonates in the 2-year pre-QI period were compared with 135 neonates in the 2 years after guideline implementation.

7. frontiersin.org frontiersin.org/journals/pain-research/articles/10.3389/fpain.2021.770511/full

Dexmedetomidine Use in Infants Undergoing Cooling Due ... A recent study including 125 neonatal intensive care units (NICUs) demonstrated that up to 64% of neonates with HIE and treated with TH received ...

8. mdpi.com mdpi.com/2227-9067/12/2/253

Sedation and Pain Management in Neonates Undergoing ... The conclusion was that dexmedetomidine was safe and effective for sedation in neonates undergoing therapeutic hypothermia, especially non-intubated infants.