Anesthetics for Child Development Outcomes

(TREX Trial)

Not currently recruiting at 24 trial locations

Overseen By Suzette J Sheppard, Bsc (Hons)

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: Murdoch Childrens Research Institute

Must not be taking: Benzodiazepines, Ketamine, Barbiturates, others

Disqualifiers: Neurologic anomaly, Prematurity, Cardiac 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

Compensation: Varies

Number of Visits: 2

Duration: 150 minutes

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a new mix of anesthetic drugs can improve long-term brain development in young children needing anesthesia for 2 hours or more. The study compares standard anesthesia with a new combination of sevoflurane, remifentanil, and dexmedetomidine. Researchers aim to determine if this approach better supports children's cognitive development by age three. This trial may suit children under 2 years old scheduled for surgery requiring at least 2 hours of anesthesia and who meet other specific criteria. As a Phase 3 trial, it represents the final step before FDA approval, offering a chance to contribute to potentially groundbreaking advancements in pediatric anesthesia.

Will I have to stop taking my current medications?

The trial protocol does not specify whether participants must stop taking their current medications. However, it does mention that planned postoperative sedation with non-opioid sedatives is not allowed, which might imply some restrictions on certain medications.

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

Research has shown that the combination of dexmedetomidine, remifentanil, and sevoflurane is generally safe for children. Studies have found that young children receiving general anesthesia with sevoflurane do not exhibit differences in IQ or behavior at about 30 months old. Specifically, one study found no negative effects in children exposed to an hour of sevoflurane compared to other types of anesthesia.

Another study confirmed that these anesthetics do not harm brain development, finding no negative impact on intelligence or behavior in children under 2 years old after surgery. Additionally, using dexmedetomidine with these anesthetics has not shown harmful effects on children's brain development.

While the effects of longer exposure remain uncertain, current research suggests that short-term use of these anesthetics is safe for children's brain development. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a potentially safer way to manage anesthesia in children, which is crucial for their development. Unlike the standard of care, which often relies on higher concentrations of sevoflurane, this trial explores the combination of dexmedetomidine and remifentanil with a lower dose of sevoflurane. Dexmedetomidine provides sedative effects with less impact on respiratory function, while remifentanil offers rapid onset and recovery, reducing the total exposure to sevoflurane. This approach aims to minimize potential side effects on the developing brain, offering a promising alternative to current practices.

What evidence suggests that this trial's treatments could be effective for child development outcomes?

Research has shown that a combination of sevoflurane, dexmedetomidine, and remifentanil, one of the treatment arms in this trial, may protect young children's brain development during anesthesia. This combination reduces the required amount of sevoflurane, which benefits the brain. In babies, adding dexmedetomidine and remifentanil to sevoflurane did not negatively affect brain development, suggesting it might be safer for long surgeries. Another arm of this trial will study sevoflurane alone. While animal studies have raised concerns about anesthesia, human studies like PANDA and GAS have found little evidence of harm from short exposures. Overall, these findings support the potential safety and effectiveness of this anesthetic combination in protecting children's development during surgery. ^{1 3 6 7 8}

Who Is on the Research Team?

Andrew J Davidson, MD

Principal Investigator

Royal Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children under 2 years old who are scheduled for an anesthesia expected to last at least 2 hours. They must have a guardian to consent and cannot have been born prematurely, had certain surgeries, or be planned for postoperative sedation with non-opioid agents.

Inclusion Criteria

I am under 2 years old.

I have someone who can legally consent for me if I'm unable to.

My upcoming surgery is expected to last at least 2 hours under anesthesia.

Exclusion Criteria

I have a condition linked to poor brain function outcomes.

I have no health issues that prevent me from following the study's procedures.

My household speaks a language not supported by the Wechsler test.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Children are randomized to receive either a low dose sevoflurane/remifentanil/dexmedetomidine or standard dose sevoflurane anaesthetic during surgery expected to last 2 hours or longer

150 minutes

1 visit (in-person)

Post-operative Monitoring

Participants are monitored for post-operative pain and recovery, including blood pressure, heart rate, and time to recovery

60 minutes

1 visit (in-person)

Follow-up

Participants receive a neurodevelopmental assessment at 3 years of age to assess global cognitive function and other developmental outcomes

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine
• Remifentanil
• Sevoflurane

Trial Overview The study tests if a low dose combination of sevoflurane, remifentanil, and dexmedetomidine leads to better long-term cognitive outcomes compared to standard dose sevoflurane in young children requiring lengthy anesthesia.

How Is the Trial Designed?

Group I: Sevoflurane/dexmedetomidine/remifentanil Experimental Treatment 3 Interventions

Dexmedetomidine: loading dose of 1mcg/kg over 10 minutes followed by an infusion of at 1 mcg/kg/hr. Remifentanil: loading dose 1 mcg/kg over 2 minutes followed by an infusion starting at 0.1 mcg/kg/min or greater. Sevoflurane: end tidal concentration of 0.6 -0.8% or less.

Group II: Sevoflurane Active Control 1 Intervention

End tidal concentration of 2.5-3.0% or greater.

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?

Murdoch Childrens Research Institute

Lead Sponsor

Trials

90

Recruited

1,303,000+

Royal Children's Hospital

Collaborator

Trials

38

Recruited

232,000+

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

University of Texas, Southwestern Medical Center at Dallas

Collaborator

Trials

18

Recruited

21,200+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Queensland Children's Hospital

Collaborator

Trials

4

Recruited

9,700+

Perth Children's Hospital

Collaborator

Trials

3

Recruited

114,000+

Women and Children's Hospital

Collaborator

Trials

1

Recruited

450+

Istituto Giannina Gaslini

Collaborator

Trials

47

Recruited

140,000+

Published Research Related to This Trial

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39283983/

Short-term Outcomes in Infants after General Anesthesia ... Short-term Outcomes in Infants after General Anesthesia with Low-dose Sevoflurane/Dexmedetomidine/Remifentanil versus Standard-dose Sevoflurane ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03089905

A Study to Compare the Long-term Outcomes After Two ... The aim of our study is to see if a new combination of anaesthetic drugs results in a better long-term developmental outcome than the current standard of care ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40923823/?utm_source=Chrome&utm_medium=rss&utm_campaign=None&utm_content=1F5sQ8LSxW_xDvDTDvz946YugjbWf8AE2pabOCzLUzoDMqH9IF&fc=None&ff=20250912144109&v=2.18.0.post9+e462414

Effects of Dexmedetomidine-Remifentanil on ... This study aimed to assess whether the combination of dexmedetomidine and remifentanil, by reducing sevoflurane exposure, has any differential ...

4. medpagetoday.com medpagetoday.com/anesthesiology/anesthesiology/117445

Trial Supports Neurodevelopmental Safety of General ... Young children getting general anesthesia showed no difference in IQ or behavioral scores at around age 30 months whether exposed to sevoflurane ...

5. empr.com empr.com/news/no-adverse-neurodevelopmental-effects-seen-from-inhaled-anesthesia-in-those-aged-less-than-2/

No Adverse Neurodevelopmental Effects Seen From ... No adverse neurodevelopmental effects with addition of dexmedetomidine and remifentanil to sevoflurane anesthesia.

6. binasss.sa.cr binasss.sa.cr/oct25/9.pdf

Effects of Dexmedetomidine–Remifentanil on ... In humans, the general anesthesia spinal trial found no evidence for adverse outcomes in children exposed to 1 h of sevoflurane ver- sus regional anesthesia.

7. clinicalpainadvisor.com clinicalpainadvisor.com/news/no-adverse-neurodevelopmental-effects-seen-from-inhaled-anesthesia-in-children-under-2/

No Adverse Neurodevelopmental Effects Seen From ... For children younger than 2 years undergoing surgery, no adverse neurodevelopmental effects are seen with the addition of dexmedetomidine ...

8. contemporarypediatrics.com contemporarypediatrics.com/view/ji-hyun-lee-md-discusses-neurodevelopmental-risk-after-anesthesia-in-infants

Ji-Hyun Lee, MD, discusses neurodevelopmental risk after ... Ji-Hyun Lee reports that short surgical exposure to sevoflurane did not affect IQ, behavior, or language outcomes in infants and toddlers.