Child BehaviorPhase 4NASONCT02447289
Midazolam and Ketamine Effect Administered Through the Nose for Sedation of Children for Dental Treatment
A Phase 4 study testing Intranasal ketamine, Oral ketamine and Intranasal midazolam in people with Child Behavior and Dental Caries, run by Universidade Federal de Goias at 1 site in Brazil.
Trial summary
Randomised clinical trial to test the efficacy, safety and cost-effectiveness of sedatives; masked, controlled, parallel design with three arms, phase 4. Read more about this study
- Who is it for?
- Ages 2 to 6 yearsHealthy volunteers can take part
- Conditions the study is for
- Child Behavior, Dental Caries
- What is being tested?
- Intranasal ketamine, Oral ketamine and Intranasal midazolam
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteBrazil
- Study dates
- 21 May 2015to 18 Oct 2016
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 6 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- Positive or definitely positive behavior (Frankl et al, 1962) in a dental treatment session conducted by the research team
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy, Safety and Cost-effectiveness of Intranasal Sedation With Ketamine and Midazolam in Pediatric Dentistry: a Randomized Clinical Trial
Randomised clinical trial to test the efficacy, safety and cost-effectiveness of sedatives; masked, controlled, parallel design with three arms, phase 4.
Read the detailed 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.
- Conditions
- Child Behavior, Dental Caries
- Being tested
- Intranasal ketamine, Oral ketamine, Intranasal midazolam, Oral midazolam
- Keywords
- Dental caries, Moderate sedation
- Medical subject headings
- Child Behavior, Dental Caries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal ketamineDrug
Also called Ketamin S, Cristalia, São Paulo, Brazil
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 ketamineDrug
Also called Ketamin S, Cristalia, São Paulo, Brazil
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 midazolamDrug
Also called Dormire injectable solution, Cristalia, São Paulo, Brazil
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 midazolamDrug
Also called Dormire oral solution, Cristalia, São Paulo, Brazil
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
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Intranasal administration of ketamine (4.0 mg/kg, max. 100 mg) and midazolam (0.2 mg/kg, max. 5 mg) Receives: Drug: Intranasal ketamine; Drug: Intranasal midazolam |
| Comparator | Active comparator | Oral administration of ketamine (4.0 mg/kg, max. 100 mg) and midazolam (0.5 mg/kg, max. 20 mg) Receives: Drug: Oral ketamine; Drug: Oral midazolam |
| Control | Active comparator | Oral administration of midazolam (1.0 mg/kg, max. 20 mg) Receives: Drug: Oral midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Participants will be followed for the duration of the dental session, an expected average of 40 minutes
Secondary outcomes (10)
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.
Measured: Participants will be assessed for the duration of the sedative administration, an expected average of 3 minutes
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
Measured: Change from baseline in the salivary cortisol at an expected average of 40 minutes
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
Measured: Participants will be followed in video files for the duration of the dental session, an expected average of 40 minutes
Caregivers' and dentists' perceptions on sedation measured by a Visual Analogue Scale
Perception of caregivers and dentists on sedation, through self-report
Measured: During and soon after the dental session
Child's perceptions on sedation through a semi-structured interview
Child's perception concerning the dental treatment under sedation
Measured: One week after the dental session
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
Measured: 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
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
Measured: 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
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
Measured: Participants will be followed for the duration of the dental session, an expected average of 40 minutes
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
Measured: 24 hours
Cost analysis
Cost-effectiveness of different sedation protocols according to the methodology of health technologies assessment; the cost of each intervention will be compared
Measured: One year and a half
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2015 (estimated)
- Study start21 May 2015
- Primary completion11 Oct 2016
- Study completion18 Oct 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Child BehaviorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universidade Federal de Goias
- Sponsor type
- University, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Responsible party
- Principal investigator, Luciane Ribeiro de Rezende Sucasas da Costa, Universidade Federal de Goias
- Investigators
- Luciane R Costa, DDS, MS, PhD, Principal investigator, Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02447289
- Sponsor's protocol ID
- 041530
- Acronym
- NASO
- Status last verified
- Apr 2018
- First submitted
- 11 May 2015
- Last updated
- 30 Apr 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: IPD can be available as requested by the scientific journal where the manuscript is gonna be submitted
Publications
Sado-Filho J, Viana KA, Correa-Faria P, Costa LR, Costa PS. Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation. PLoS One. 2019 Mar 11;14(3):e0213074. doi: 10.1371/journal.pone.0213074. eCollection 2019.
PubMed 30856181Gomes HS, Miranda AR, Viana KA, Batista AC, Costa PS, Daher A, Machado GC, Sado-Filho J, Vieira LA, Correa-Faria P, Hosey MT, Costa LR. Intranasal sedation using ketamine and midazolam for pediatric dental treatment (NASO): study protocol for a randomized controlled trial. Trials. 2017 Apr 11;18(1):172. doi: 10.1186/s13063-017-1919-2.
PubMed 28399933
Study at a glance
From the registry record, last updated by the sponsor on 30 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety and Cost-effectiveness of Intranasal Sedation With Ketamine and Midazolam in Pediatric Dentistry: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT02447289
- Acronym / sponsor ID
- NASO / 041530
- Conditions
- Child Behavior, Dental Caries
- Keywords
- Dental caries, Moderate sedation
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Universidade Federal de GoiasUniversity, hospital or other
- Collaborators
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Study start
- 21 May 2015 (actual)
- Primary completion
- 11 Oct 2016 (actual)
- Study completion
- 18 Oct 2016 (actual)
- First posted
- 18 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Randomised clinical trial to test the efficacy, safety and cost-effectiveness of sedatives; masked, controlled, parallel design with three arms, phase 4.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: Intranasal ketamine, Drug: Intranasal midazolamIntranasal administration of ketamine (4.0 mg/kg, max. 100 mg) and midazolam (0.2 mg/kg, max. 5 mg) |
| Comparator | Active comparator | Drug: Oral ketamine, Drug: Oral midazolamOral administration of ketamine (4.0 mg/kg, max. 100 mg) and midazolam (0.5 mg/kg, max. 20 mg) |
| Control | Active comparator | Drug: Oral midazolamOral administration of midazolam (1.0 mg/kg, max. 20 mg) |
Who may qualify
- Ages
- 2 to 6 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (1 listed)
- Positive or definitely positive behavior (Frankl et al, 1962) in a dental treatment session conducted by the research team
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intranasal ketamineAlso: Ketamin S, Cristalia, São Paulo, BrazilKetamine 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 | Drug | Experimental |
| Oral ketamineAlso: Ketamin S, Cristalia, São Paulo, BrazilKetamine injectable solution in a concentration of 50.0 mg/mL via oral route; dose of 4.0 mg/kg maximum 100.0 mg | Drug | Comparator |
| Intranasal midazolamAlso: Dormire injectable solution, Cristalia, São Paulo, BrazilMidazolam 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 | Drug | Experimental |
| Oral midazolamAlso: Dormire oral solution, Cristalia, São Paulo, BrazilMidazolam 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 | Drug | Comparator, Control |
Primary outcome
Child's behavior measured by an observational scale
Time frame: Participants will be followed for the duration of the dental session, an expected average of 40 minutes
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.
10 secondary outcomes
Acceptance of sedative administration measured by an observational scale
Time frame: Participants will be assessed for the duration of the sedative administration, an expected average of 3 minutes
Participants' stress according to salivary cortisol
Time frame: Change from baseline in the salivary cortisol at an expected average of 40 minutes
Pain measured by the FLACC Pain Assessment Tool
Time frame: Participants will be followed in video files for the duration of the dental session, an expected average of 40 minutes
Caregivers' and dentists' perceptions on sedation measured by a Visual Analogue Scale
Time frame: During and soon after the dental session
Child's perceptions on sedation through a semi-structured interview
Time frame: One week after the dental session
Memory of the dental procedure at the immediate post-operative period measured by a validated test
Time frame: 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
Memory of the dental procedure after 24 hours measured by a validated test
Time frame: 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
Adverse events during the dental procedure
Time frame: Participants will be followed for the duration of the dental session, an expected average of 40 minutes
Post-operative adverse events
Time frame: 24 hours
Cost analysis
Time frame: One year and a half
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Apr 2018.
- Derived from this study: PubMed 30856181Sado-Filho J, Viana KA, Correa-Faria P, Costa LR, Costa PS. Randomized clinical trial on the efficacy of intranasal or oral ketamine-midazolam combinations compared to oral midazolam for outpatient pediatric sedation. PLoS One. 2019 Mar 11;14(3):e0213074. doi: 10.1371/journal.pone.0213074. eCollection 2019.
- Derived from this study: PubMed 28399933Gomes HS, Miranda AR, Viana KA, Batista AC, Costa PS, Daher A, Machado GC, Sado-Filho J, Vieira LA, Correa-Faria P, Hosey MT, Costa LR. Intranasal sedation using ketamine and midazolam for pediatric dental treatment (NASO): study protocol for a randomized controlled trial. Trials. 2017 Apr 11;18(1):172. doi: 10.1186/s13063-017-1919-2.
- Individual participant dataSharing planned: Undecided. IPD can be available as requested by the scientific journal where the manuscript is gonna be submitted
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Luciane R Costa, DDS, MS, PhD principal investigator
Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intranasal ketamine, Oral ketamine and Intranasal midazolam in people with Child Behavior and Dental Caries, run by Universidade Federal de Goias at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Child's behavior measured by an observational scale (time frame: Participants will be followed for the duration of the dental session, an expected average of 40 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02447289, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Apr 2018.