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

Trial Summary

What is the purpose of this trial?

Neonatal intubations are performed routinely in a NICU. Most intubations are still performed without the administration of medications (awake intubations). Some of the reasons are unavailability of a single good medication, the ease of administration, the physicians comfort level, side effects of medications including apnea, bradycardia, hypotension. Some units use a cocktail of different medications, each with their own side effects We are proposing to study the effects of a single medication, dexmedetomidine (precedex) for the purpose of sedation prior to intubation in neonates. This study will compare the efficacy of a single dose of dexmedetomidine to controls.

Will I have to stop taking my current medications?

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

What data supports the effectiveness of the drug Dexmedetomidine for neonatal sedation?

Dexmedetomidine has been shown to provide effective sedation in children undergoing procedures, allowing them to breathe on their own without needing a breathing tube. It is also used safely in pediatric patients for various procedures, providing smooth sedation with minimal breathing issues. ^{1 2 3 4 5}

Is dexmedetomidine safe for use in neonates and children?

Dexmedetomidine has been shown to be safe in the short term for neonates and children, with common side effects including slow heart rate (bradycardia) and low blood pressure (hypotension). It is well-tolerated in pediatric patients for sedation during procedures, but more studies are needed to understand its long-term safety. ^{1 3 5 6 7}

How is the drug Dexmedetomidine unique for neonatal sedation?

Dexmedetomidine is unique for neonatal sedation because it works by activating certain receptors in the brain that help calm and sedate without causing significant respiratory depression, which is a common risk with other sedatives. This makes it potentially safer for use in newborns compared to traditional sedatives. ^{8 9 10 11 12}

Research Team

Alok Bhutada, MD

Principal Investigator

Maimonides Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 (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]

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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Patients Undergoing Procedure-Type Sedation. [2020]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a guide to its use for sedation in the US. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Dexmedetomidine use in pediatric airway reconstruction. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine versus standard therapy with fentanyl for sedation in mechanically ventilated premature neonates. [2022]

5. France pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine - An emerging option for sedation in neonatal patients. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

Sodium oxybate for narcolepsy. [2015]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of the Effectiveness of the Risk Minimization Measures of Sodium Oxybate in the European Union. [2020]

10. Switzerland 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. [2021]

11. New Zealand pubmed.ncbi.nlm.nih.gov

Sodium oxybate: a review of its use in the management of narcolepsy. [2019]

12. United States 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. [2023]