Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment

Dental Caries Clinical Trial

— NASO  

Official title:

Efficacy, Safety and Cost-effectiveness of Intranasal Sedation With Ketamine and Midazolam in Pediatric Dentistry: a Randomized Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02447289
• Other study ID #: 041530
• Status: Completed
• Phase: Phase 4
• Start date: May 21, 2015
• Est. completion date: October 18, 2016

Study information

• Verified date: April 2018
• Source: Universidade Federal de Goias
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomised clinical trial to test the efficacy, safety and cost-effectiveness of sedatives; masked, controlled, parallel design with three arms, phase 4.

Description:

About 10% of children may have behavioral problems during dental treatment, but the evidence for sedative protocols that benefit the care in pediatric dentistry are still weak. This randomized, masked, controlled, parallel design study aims to evaluate the efficacy, safety and cost-effectiveness of intranasal sedation with ketamine / midazolam in healthy children aged 2 to 6 years old. Children will be selected among those with dental decay that do not allow dental treatment to be performed, and need at least two restorations under local anesthesia and rubber dam isolation. It is estimated a preliminarily a sample of 84 children equally divided into three groups: A) Ketamine (4.0 mg / kg up to 100 mg) + midazolam (0.2 mg / kg, maximum 5 mg) intranasally; B) ketamine (4.0 mg / kg up to 100 mg) + midazolam (0.5 mg / kg, maximum 20 mg) orally; C) midazolam (1.0 mg / kg, maximum 20 mg) orally. The hypothesis is that ketamine / midazolam combination, administered intranasally, it constitutes an effective sedative regime, safe and cost-effective for use in pediatric dentistry in the public service. The primary endpoint is the behavior of the child. Secondary endpoints are: sedative administration acceptance, procedure memory and salivary cortisol levels within each intervention group. Additionally, we will evaluate: the occurrence of pain and associated changes in facial expressions with potentially painful stimuli in children sedated for dental care; caregivers and paediatric dentists' stress and perception about sedation; adverse events that occur during and after administration of sedatives; cost-effectiveness of the sedative protocols. The experimental design is planned to minimize systematic and random errors and to contribute to higher level of evidence in future systematic reviews. The outcomes of this study have potential impact on public and private health practice, and may support institutional guidelines dealing with this theme.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: October 18, 2016
• Est. primary completion date: October 11, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 2 Years to 6 Years

Eligibility

Inclusion Criteria:

• American Society of Anesthesiologists I (healthy) or II (mild and controlled systemic disease such as persistent asthma)

• Small risk of airway obstruction (Mallampati less than 2 or tonsillar hypertrophy occupying less than 50% of the oropharynx)

• No medical history of neurological or cognitive changes

• Absence of facial deformities

• Term birth

• No use of drugs that may impair cognitive functions

• At least two teeth with cavities without pulp involvement, requiring dental restoration under local anesthesia and rubber dam

Exclusion Criteria:

• Positive or definitely positive behavior (Frankl et al, 1962) in a dental treatment session conducted by the research team

Related Conditions & MeSH terms

• Child Behavior
• Dental Caries

Intervention

Drug:
• Intranasal ketamine
Ketamine injectable solution in a concentration of 50.0 mg/mL administered into the nose with an atomizer; dose of 4.0 mg/kg, maximum 100.0 mg
• Oral ketamine
Ketamine injectable solution in a concentration of 50.0 mg/mL via oral route; dose of 4.0 mg/kg maximum 100.0 mg
• Intranasal midazolam
Midazolam injectable solution in a concentration of 5.0 mg/mL administered into the nose with an atomizer; dose of 0.2 mg/kg, maximum 5.0 mg
• Oral midazolam
Midazolam oral solution in a concentration of 2.0 mg/mL via oral route; dose of 0.5 mg/kg, maximum 5.0 mg when associated with ketamine; dose of 1.0 mg/kg, maximum 20.0 mg when give as a solely agent

Locations

Country	Name	City	State
Brazil	Dental School	Goiania	Goias

Sponsors (2)

Lead Sponsor	Collaborator
Universidade Federal de Goias	Conselho Nacional de Desenvolvimento Científico e Tecnológico

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Child's behavior measured by an observational scale	Children's behavior assessed by OSUBRS (Ohio State University Behavioral Rating Scale) in digital videos recorded during the administration. Scores: 1 - quiet, 2 - cry with movement, 3 - movement without cry; 4 - struggling. Satisfactory behavior means more than 60% of score 1 during the entire appointment.	Participants will be followed for the duration of the dental session, an expected average of 40 minutes
Secondary	Acceptance of sedative administration measured by an observational scale	Acceptance of the sedative administration, assessed by OSUBRS (Ohio State University Behavioral Rating Scale) minute by minute in digital videos recorded during the administration. Scores: 1 - quiet, 2 - cry with movement, 3 - movement without cry; 4 - struggling.	Participants will be assessed for the duration of the sedative administration, an expected average of 3 minutes
Secondary	Participants' stress according to salivary cortisol	Occurrence of stress during dental procedure, assessed by salivary cortisol in children, their accompanying parent and the dentist in charge; the ELISA test will determine changes in cortisol level during dental treatment	Change from baseline in the salivary cortisol at an expected average of 40 minutes
Secondary	Pain measured by the FLACC Pain Assessment Tool	Occurrence of pain and associated changes in body expressions with potentially painful stimuli in children sedated for dental care	Participants will be followed in video files for the duration of the dental session, an expected average of 40 minutes
Secondary	Caregivers' and dentists' perceptions on sedation measured by a Visual Analogue Scale	Perception of caregivers and dentists on sedation, through self-report	During and soon after the dental session
Secondary	Child's perceptions on sedation through a semi-structured interview	Child's perception concerning the dental treatment under sedation	One week after the dental session
Secondary	Memory of the dental procedure at the immediate post-operative period measured by a validated test	Memory of the dental procedure, according to test with figures validated in Brazil. Amnesia will be reported if children do not recall the figures showed after sedative administration	Participants will be assessed for the recall of the dental procedure, at a time point of 20 minutes (average) after the end of the dental procedure
Secondary	Memory of the dental procedure after 24 hours measured by a validated test	Memory of the dental procedure, according to test with figures validated in Brazil. Amnesia will be reported if children do not recall the figures showed after sedative administration	Participants will be assessed for the recall of the dental procedure, at a time point of 24 hours (average) after the end of the dental procedure
Secondary	Adverse events during the dental procedure	Occurrence of adverse events assessed by the World SIVA tool; adverse events will be categorised into minor, sentinel and major	Participants will be followed for the duration of the dental session, an expected average of 40 minutes
Secondary	Post-operative adverse events	Occurrence of adverse events while child is in the recovery room and after discharge, assessed by the World SIVA tool; adverse events will be categorised into minor, sentinel and major	24 hours
Secondary	Cost analysis	Cost-effectiveness of different sedation protocols according to the methodology of health technologies assessment; the cost of each intervention will be compared	One year and a half