Dexmedetomidine for Neonatal Sedation

Overseen By Anju Gupta-Modak, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Maimonides Medical Center

Disqualifiers: Emergent intubation, Low birth weight, Congenital malformations, Hypotension, Heart disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of dexmedetomidine (also known as Precedex), a sedative, for calming newborns before intubation. Intubation involves placing a tube into the windpipe to assist breathing. Currently, many newborns in the NICU (Neonatal Intensive Care Unit) undergo intubation while awake, which can be stressful and uncomfortable. The study compares this sedative to standard methods to determine if it makes the process smoother and safer. Eligible newborns are those in the NICU needing planned intubation and are less than 44 weeks in corrected gestational age. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment for newborns.

Will I have to stop taking my current medications?

The trial information does not specify whether participants must stop taking their current medications.

Is there any evidence suggesting that dexmedetomidine is likely to be safe for neonates?

Research has shown that dexmedetomidine is generally safe for newborns. In studies, babies experienced fewer side effects with dexmedetomidine compared to other common sedatives. Observational studies also found that dexmedetomidine can reduce the need for stronger medications like opioids and benzodiazepines, which are often used for sedation. These studies did not report any major problems when dexmedetomidine was administered in appropriate amounts to newborns.

However, limited information exists on the long-term effects of dexmedetomidine in newborns. While it appears safe in the short term, more research is needed to understand its long-term effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Dexmedetomidine is unique because it offers a potentially safer and more comfortable option for neonatal sedation compared to current practices like awake intubation. Unlike most standard treatments that might involve more invasive methods or medications with greater side effects, dexmedetomidine is administered as a single intravenous dose and is known for its sedative and pain-relieving properties without causing significant respiratory depression. Researchers are excited about dexmedetomidine because it has the potential to provide effective sedation while minimizing stress and discomfort for newborns, which is crucial for their delicate development.

What evidence suggests that dexmedetomidine might be an effective treatment for neonatal sedation?

Research shows that dexmedetomidine, which participants in this trial may receive, is a promising choice for calming newborns. It is considered safer than morphine and other strong painkillers often used for babies. Dexmedetomidine has little effect on breathing, which is crucial for newborns. Studies have also found that it can help babies spend less time on a breathing machine and require fewer additional calming medicines. While some research has mixed results, the overall evidence supports its effectiveness in calming newborns. ^{1 2 4 5 6}

Who Is on the Research Team?

Alok Bhutada, MD

Principal Investigator

Maimonides Medical Center

Are You a Good Fit for This Trial?

This trial is for neonates admitted to the NICU who need elective intubation and are less than 44 weeks corrected gestational age. It's not for babies under 1250 grams or less than a week old, those with major birth defects, preexisting low blood pressure (MAP < Gest Age), complex heart issues, or if they need emergency intubation.

Inclusion Criteria

Neonates admitted to the NICU

My newborn needs a planned breathing tube insertion.

My newborn requires breathing support and is under 44 weeks in corrected gestational age.

Exclusion Criteria

My newborn has a complex heart condition and heart block.

My newborn weighs less than 1250 grams and is under 1 week old.

My newborn needs immediate help to breathe.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single intravenous dose of dexmedetomidine or undergo routine awake intubation

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 minutes

Continuous monitoring during and after intubation

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine

Trial Overview The study tests whether dexmedetomidine (precedex) is effective as sedation before putting a tube in a baby's windpipe compared to usual care without medication. Babies will be randomly assigned to receive either the drug or no sedative.

How Is the Trial Designed?

Group I: Control Group Active Control 1 Intervention

routine awake intubation as per current unit standard of care

Group II: Dexmedetomidine Group Active Control 1 Intervention

a single intravenous (i.v.) dose of dexmedetomidine, 0.2 mcg/kg over 10 minutes

Dexmedetomidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in United States as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Canada as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Japan as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Who Is Running the Clinical Trial?

Maimonides Medical Center

Lead Sponsor

Trials

72

Recruited

15,400+

Published Research Related to This Trial

Sodium oxybate (Xyrem) is the only FDA-approved treatment specifically for cataplexy in narcolepsy and has recently been approved for excessive daytime sleepiness associated with the condition.

Unlike traditional antidepressants and stimulants, sodium oxybate effectively addresses both cataplexy and daytime sleepiness with a lower risk of tolerance and side effects when used correctly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy. Scharf, MB.[2015]

Sodium oxybate (Xyrem) is an effective treatment for narcolepsy, specifically reducing cataplexy and excessive daytime sleepiness, and is generally well tolerated by patients.

Despite its short half-life requiring twice-nightly dosing, sodium oxybate provides a valuable alternative to traditional treatments like TCAs, SSRIs, and stimulants for managing narcolepsy symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium oxybate: a review of its use in the management of narcolepsy. Robinson, DM., Keating, GM.[2019]

In a study involving 91 pediatric patients, dexmedetomidine was found to be a well-tolerated alternative sedative for non-intubated moderate or deep sedation, with a low incidence of serious adverse events.

While respiratory depression and hypotension were the most common treatment-emergent adverse events, they were manageable and consistent with dexmedetomidine's known safety profile, indicating its potential for safe use in children during elective procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. Jooste, EH., Hammer, GB., Reyes, CR., et al.[2020]

Intravenous dexmedetomidine is effective for sedation in mechanically ventilated patients and during procedures, reducing the need for additional sedatives like propofol or midazolam.

It is generally well tolerated, does not cause respiratory depression, and while it may lead to hypotension and bradycardia, these side effects typically resolve on their own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a guide to its use for sedation in the US. Keating, GM., Hoy, SM., Lyseng-Williamson, KA.[2022]

Dexmedetomidine was found to be more effective than fentanyl for sedation in mechanically ventilated premature neonates, requiring less additional sedation and resulting in a shorter duration of mechanical ventilation (14.4 days vs. 28.4 days).

The use of dexmedetomidine also led to quicker recovery metrics, such as earlier meconium passage and faster achievement of full enteral feeds, along with a lower incidence of culture-positive sepsis compared to fentanyl.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine versus standard therapy with fentanyl for sedation in mechanically ventilated premature neonates. O'Mara, K., Gal, P., Wimmer, J., et al.[2022]

Dexmedetomidine was safely used to sedate a pediatric patient during 12 radiation therapy sessions, demonstrating its effectiveness as a sedative and anesthetic adjuvant.

The use of dexmedetomidine resulted in smooth induction and quick recovery while causing minimal respiratory depression, highlighting its favorable safety profile in pediatric sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as the primary sedative agent for brain radiation therapy in a 21-month old child. Shukry, M., Ramadhyani, U.[2013]

Dexmedetomidine has been shown to be effective and generally safe for short-term use in neonates, based on a review of 21 studies and 1 case report.

The recommended dosing for dexmedetomidine in neonates ranges from 0.5 to 1.5 mcg/kg/h, but caution is advised due to potential adverse effects like bradycardia and hypotension, highlighting the need for further research on long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine - An emerging option for sedation in neonatal patients. McDonald, D., Palsgraf, H., Shah, P.[2022]

Dexmedetomidine is a promising sedative for children in intensive care, showing efficacy in reducing the need for other sedatives and being particularly beneficial for those with neurologic impairments.

While generally well tolerated, dexmedetomidine can cause hypotension and bradycardia in 10% to 20% of patients, necessitating careful monitoring during its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine use in pediatric intensive care and procedural sedation. Buck, ML.[2022]

Sodium oxybate (SXB) maintained its long-term efficacy in reducing weekly cataplexy attacks and improving sleepiness in children and adolescents (ages 7-16) with narcolepsy with cataplexy, as shown in a study involving 106 participants, with 85 completing the open-label period.

The safety profile of SXB in this pediatric population was consistent with that observed in adults, with common side effects including enuresis, nausea, and headache, indicating it is a viable treatment option for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and maintenance of efficacy of sodium oxybate in the treatment of narcolepsy with cataplexy in pediatric patients. Lecendreux, M., Plazzi, G., Dauvilliers, Y., et al.[2023]

In a study of 24 pediatric patients undergoing airway reconstruction, dexmedetomidine was found to be well tolerated and safe, particularly for short-term intubation, with no significant adverse effects reported.

Dexmedetomidine may serve as a beneficial alternative to propofol for sedation during the periextubation period, allowing for easily reversible sedation, although further research is needed to explore its long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine use in pediatric airway reconstruction. Silver, AL., Yager, P., Purohit, P., et al.[2022]

A survey of 31 healthcare professionals revealed that while most received safety information about sodium oxybate (Xyrem®), only a small number recalled receiving educational materials, indicating a gap in effective communication regarding its risks and usage.

Despite the limited sample size, the majority of respondents demonstrated a good understanding of dosing and contraindications, highlighting the need for improved educational outreach to enhance knowledge about the drug's potential for misuse and adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the Effectiveness of the Risk Minimization Measures of Sodium Oxybate in the European Union. Iranzo, A., Serralheiro, P., Schuller, JC., et al.[2020]

Sodium oxybate, used for treating narcolepsy, is tightly controlled under the Xyrem REMS Program, which ensures safe prescribing and distribution, with 17,037 patients receiving shipments during the study period.

The program effectively monitored for potential abuse and misuse, reporting low rates of lost shipments (0.009%) and high awareness of safety risks among patients and prescribers, although further education for prescribers on these risks may be beneficial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Xyrem&#174; (Sodium Oxybate) Risk Evaluation and Mitigation Strategy (REMS) Program in the USA: Results From 2016 to 2017. Strunc, MJ., Black, J., Lillaney, P., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38695625/

Dexmedetomidine for analgesia and sedation in newborn ... It is thought to be safer than morphine or stronger opioids, which are drugs currently used for analgesia and sedation in newborn infants.

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

Dexmedetomidine in neonates: utilisation trends and safety ... Dexmedetomidine has been considered a promising option for neonatal sedation and analgesia because of its minimal depressant effects on the respiratory and ...

3. mdpi.com mdpi.com/2227-9067/12/4/444

Shifting Paradigms in Neonatal Sedation and Pain Control Research across varying age groups has demonstrated that dexmedetomidine shortens periods of invasive ventilation and decreases the need for other sedatives.

4. ascpt.onlinelibrary.wiley.com ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.70020

A systematic review of dexmedetomidine pharmacology in ... These studies provide contradictory results, with reduced sedation (i.e. reduced efficacy) in one cohort, but increased bradycardia ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06878703

Efficacy of Dexmedetomidine Versus Midazolam Sedation ... Specifically, investigators aim to determine whether DEX can facilitate more rapid extubation and better overall respiratory outcomes compared to midazolam. By ...

6. asclepiushealthjournal.com asclepiushealthjournal.com/index.php/aijshs/article/view/312

DEXMEDETOMIDINE IN NEONATAL SEDATION AND ... Results and Discussion: Observational and implementation studies suggest dexmedetomidine can reduce exposure to opioids and benzodiazepines in ...