Sedatives for Anxiety with Lacerations in Children

(ALICE Trial)

Overseen By Naveen Poonai, MD

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Must not be taking: Sedatives, Anxiolytics, Alpha-2 agonists

Disqualifiers: Pregnancy, Renal insufficiency, Psychosis, 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

300 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests three ways to help calm children during stitches: two nose sprays (dexmedetomidine and midazolam) and a gas (nitrous oxide). It focuses on children who need stitches because they often feel very distressed. These methods work by making children feel sleepy or reducing their pain. Dexmedetomidine has been studied for its effectiveness in reducing agitation after tonsillectomy in children.

Will I have to stop taking my current medications?

The trial requires that participants do not take any sedative, anxiolytic, or alpha-2-adrenergic receptor agonist within 24 hours before the intervention. This means you may need to stop certain medications that fall into these categories before participating.

What data supports the effectiveness of the drug for anxiety in children with lacerations?

Research shows that intranasal midazolam and dexmedetomidine are effective in reducing anxiety in children during medical procedures. Midazolam is known for its calming effects, while dexmedetomidine is safe and effective when used with nitrous oxide for sedation. ^{1 2 3 4 5}

Is the combination of sedatives like dexmedetomidine, midazolam, and nitrous oxide safe for children?

Studies suggest that using dexmedetomidine or midazolam with nitrous oxide is generally safe for children, with no major adverse events reported. Some children experienced minor issues like low blood pressure or increased heart rate, but these did not require medical intervention. ^{1 3 6 7 8}

How does this drug differ from other treatments for anxiety in children with lacerations?

This treatment is unique because it combines intranasal dexmedetomidine and midazolam, which are both effective in reducing anxiety, with nitrous oxide, a gas that provides quick sedation. This combination offers a flexible approach to managing anxiety and sedation in children, potentially improving comfort and cooperation during laceration repair. ^{2 4 9 10 11}

Eligibility Criteria

This trial is for children aged 2 to nearly 13 years who need stitches for a single cut and don't require heavy sedation. The child or caregiver must want mild sedation, which will be given alongside local anesthesia. Kids with certain heart rates or blood pressure issues, suspected pregnancy, inability to express pain, language barriers without an interpreter, over 65 kg in weight, not healthy or with controlled disease only (ASA class I/II), drug allergies or recent sedatives can't join.

Inclusion Criteria

My cut is simple and doesn't need strong sedation for repair.

I am between 2 and 12 years old.

My wound was stitched by an emergency doctor or their trainee.

Exclusion Criteria

Hypersensitivity to any intervention

Hemodynamic abnormalities: bradycardia or hypotension < 2 SD of age-related normal value

One of my nostrils is blocked, possibly affecting medication absorption.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparation and Treatment

Participants receive anxiolytic treatment (IN dexmedetomidine, IN midazolam, or N2O) for laceration repair

40 minutes

1 visit (in-person)

Recovery

Participants are monitored post-procedure for any immediate adverse effects and satisfaction is assessed

40 minutes

1 visit (in-person)

Follow-up

Participants are monitored for late maladaptive behaviors and any adverse effects up to 72 hours post-discharge

72 hours

Treatment Details

Interventions

• Dexmedetomidine
• Midazolam Nasal Spray
• Nitrous oxide

Trial Overview The study tests three light sedatives: dexmedetomidine and midazolam as nasal sprays, and nitrous oxide gas. It aims to find the best one for calming kids during stitch application after cuts. Children are randomly assigned to receive one of these treatments and their distress levels are measured using the OSBD-R scale.

Participant Groups

Group I: Intranasal midazolam Experimental Treatment 1 Intervention

IN midazolam 0.4 mg/kg \[5 mg/mL (max 10 mg or 2 mL)\]

Group II: Intranasal dexmedetomidine Experimental Treatment 1 Intervention

IN dexmedetomidine 3 mcg/kg \[100 mcg/mL (max 200 mcg or 2 mL)\]

Group III: Inhaled nitrous oxide Experimental Treatment 1 Intervention

50% N2O in 50% oxygen by face mask or on-demand system

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?

London Health Sciences Centre OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

668

Recruited

424,000+

London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

678

Recruited

421,000+

London Health Sciences Centre Research Institute and Lawson Research Institute of St. Joseph's

Lead Sponsor

Trials

686

Recruited

427,000+

Lawson Health Research Institute

Lead Sponsor

Trials

684

Recruited

432,000+

Findings from Research

A study involving 149 healthy children aged 3 to 6 years found that intranasal dexmedetomidine combined with nitrous oxide is a safe sedation option for dental procedures, with no major adverse events reported.

While all sedation regimens, including oral midazolam combinations, resulted in some hypotension, only one case of bradycardia occurred with dexmedetomidine, and no interventions were needed, indicating overall safety across the groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Retrospective Evaluation of the Safety Profile of Dexmedetomidine and Nitrous Oxide for Pediatric Dental Sedation. Unkel, JH., Cruise, C., Rice, A., et al.[2021]

In a study of 40 pediatric patients aged 1-5 years undergoing laceration repairs, intranasal dexmedetomidine significantly reduced anxiety scores at the time of positioning for the procedure compared to intranasal midazolam, with a median difference of 9.2 points.

Dexmedetomidine was associated with a higher proportion of patients classified as not anxious (70%) compared to midazolam (11%) at the time of positioning, indicating it may be a more effective anxiolytic for this specific situation, with no serious adverse events reported in either group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind Randomized Controlled Trial of Intranasal Dexmedetomidine Versus Intranasal Midazolam as Anxiolysis Prior to Pediatric Laceration Repair in the Emergency Department. Neville, DN., Hayes, KR., Ivan, Y., et al.[2018]

In a study involving child patients receiving nitrous oxide sedation, intranasal midazolam (0.1 mg/kg) significantly improved acceptance of the nasal hood compared to a normal saline control, with a p-value of 0.002308 indicating strong statistical significance.

The combination of midazolam and nitrous oxide resulted in good to excellent behavior in children who were initially anxious, suggesting that midazolam is an effective premedication for reducing anxiety during dental procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal Midazolam Premedication for Anxiolysis in Children Reluctant to Receive Nitrous Oxide Sedation via Nasal Hood: An In Vivo Randomized Control Trial. Musani, I., Bhure, S., Choubey, S., et al.[2022]

Midazolam is a safe and effective option for reducing anxiety in children under 6 during laceration repair, especially when administered orally or intranasally.

Traditional sedation methods like nitrous oxide and intramuscular cocktails have various drawbacks, making Midazolam a preferable choice in emergency settings for young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Which sedation for minor trauma surgery in children?]. De Guio, G., Bartier, JC.[2014]

In a study involving 84 uncooperative pediatric dental patients aged 4-14, intranasal Dexmedetomidine showed the highest overall success rate for sedation at 85.7%, compared to Midazolam (61.9%) and Ketamine (66.7%), although differences were not statistically significant.

All three medications (Dexmedetomidine, Midazolam, and Ketamine) were found to be safe, with no significant adverse effects reported, but Dexmedetomidine caused a notable reduction in pulse rate and systolic blood pressure compared to the other drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparative evaluation of intranasal dexmedetomidine, midazolam and ketamine for their sedative and analgesic properties: a triple blind randomized study. Surendar, MN., Pandey, RK., Saksena, AK., et al.[2022]

Intranasal dexmedetomidine (1 μg/kg) provided significantly better sedation scores than oral midazolam (0.5 mg/kg) during separation and induction in children undergoing elective lower abdominal surgery, indicating its efficacy as a premedication option.

Despite differences in heart rate and blood pressure observed with dexmedetomidine, these changes did not require medical intervention, suggesting a favorable safety profile compared to midazolam.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of intranasal dexmedetomidine versus oral midazolam for paediatric premedication. Kumar, L., Kumar, A., Panikkaveetil, R., et al.[2020]

Intranasal midazolam (0.1 mg/kg) combined with nitrous oxide-oxygen sedation has a significantly quicker onset of sedation (average 12.1 minutes) compared to oral midazolam (0.2 mg/kg) which takes about 20.1 minutes, making it a faster option for uncooperative children during dental procedures.

Both methods showed good acceptability and effectiveness, but intranasal midazolam resulted in higher alertness post-sedation, suggesting a quicker recovery, and it is effective at a lower dosage than the oral route.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the sedative effect of oral versus nasal midazolam combined with nitrous oxide in uncooperative children. Musani, IE., Chandan, NV.[2022]

In a study involving 35 anxious children aged 4 to 8 years, intranasal midazolam provided a faster onset of sedation compared to nitrous oxide, making it an effective option for managing dental anxiety.

Both sedation methods were found to be safe, with no significant differences in recovery time or adverse reactions, indicating that intranasal midazolam is a viable alternative to nitrous oxide for dental procedures in anxious children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and physiologic effects of intranasal midazolam and nitrous oxide inhalation based sedation in children visiting Saveetha Dental College and Hospitals, India. Ann Preethy, N., Somasundaram, S.[2023]

In a clinical trial involving children under 6 years old, a single oral dose of midazolam (0.2 mg/kg) significantly reduced anxiety during laceration repair, with 70% of children showing a two-point or more decrease in anxiety levels compared to only 12% in the placebo group.

Midazolam was found to be safe, with no reported respiratory depression or complications, making it an effective option for managing anxiety in young children undergoing medical procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of oral midazolam on anxiety of preschool children during laceration repair. Hennes, HM., Wagner, V., Bonadio, WA., et al.[2019]

In a study of 204 children aged 2 to 6 years undergoing laceration repair, the use of continuous-flow nitrous oxide significantly reduced anxiety and distress compared to oral midazolam, as measured by the Observational Scale of Behavioral Distress-Revised (OSBD-R).

Children receiving midazolam experienced more adverse effects and longer recovery times, indicating that nitrous oxide is a safer and more effective option for managing anxiety during minor surgical procedures in young children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. Luhmann, JD., Kennedy, RM., Porter, FL., et al.[2022]

In a study of 40 young children receiving intranasal midazolam for laceration repair, 73% achieved adequate sedation, with higher doses (0.3 to 0.5 mg/kg) leading to better sedation outcomes compared to lower doses (0.2 to 0.29 mg/kg).

The sedation onset was quick, occurring within about 12 minutes, and the treatment was found to be safe, with no significant side effects like vomiting or oxygen desaturation observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal midazolam as a sedative for children during laceration repair. Yealy, DM., Ellis, JH., Hobbs, GD., et al.[2022]

References

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

A Retrospective Evaluation of the Safety Profile of Dexmedetomidine and Nitrous Oxide for Pediatric Dental Sedation. [2021]

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

Double-blind Randomized Controlled Trial of Intranasal Dexmedetomidine Versus Intranasal Midazolam as Anxiolysis Prior to Pediatric Laceration Repair in the Emergency Department. [2018]

3. India pubmed.ncbi.nlm.nih.gov

Intranasal Midazolam Premedication for Anxiolysis in Children Reluctant to Receive Nitrous Oxide Sedation via Nasal Hood: An In Vivo Randomized Control Trial. [2022]

4. France pubmed.ncbi.nlm.nih.gov

[Which sedation for minor trauma surgery in children?]. [2014]

5. Singapore pubmed.ncbi.nlm.nih.gov

A comparative evaluation of intranasal dexmedetomidine, midazolam and ketamine for their sedative and analgesic properties: a triple blind randomized study. [2022]

6. India pubmed.ncbi.nlm.nih.gov

Efficacy of intranasal dexmedetomidine versus oral midazolam for paediatric premedication. [2020]

7. England pubmed.ncbi.nlm.nih.gov

A comparison of the sedative effect of oral versus nasal midazolam combined with nitrous oxide in uncooperative children. [2022]

8. Singapore pubmed.ncbi.nlm.nih.gov

Safety and physiologic effects of intranasal midazolam and nitrous oxide inhalation based sedation in children visiting Saveetha Dental College and Hospitals, India. [2023]

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

The effect of oral midazolam on anxiety of preschool children during laceration repair. [2019]

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

A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair. [2022]

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

Intranasal midazolam as a sedative for children during laceration repair. [2022]