ED50 and ED95 of Intranasal Dexmedetomidine in Pediatric Patients Undergoing Transthoracic Echocardiography Study

Study Overview
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Brief Summary
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The median effective dose (ED50) and ED95 of intranasal dexmedetomidine as a single bolus have not been described for sedation in children undergoing transthoracic echocardiography (TEE) study. This information is important to compare agents and to determine the most effective sedative dose. The investigators performed a two-stage study to determine the ED50 and the ED95 of intranasal dexmedetomidine to investigate age-related differences in participants undergoing transthoracic echocardiography study.

Detailed Description
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The investigators performed a two-stage study to determine the ED50 and the ED95 of intranasal dexmedetomidine in children undergoing transthoracic echocardiography study. In phase 1, 120 participants were randomized in a Dixon-Massey study to describe the minimum local sedative dose. In phase 2, a further 160 participants were randomly allocated to receive sedation with doses in the upper dose-response range to define the ED95

Official Title
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ED50 and ED95 of Intranasal Dexmedetomidine in Pediatric Patients Undergoing Transthoracic Echocardiography Study

Conditions
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Patients for Transthoracic Echocardiography, Unknown Diagnosis

Intervention / Treatment
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* Drug: intranasal dexmedetomidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children, aged between one and 24 months. classified as (American Society of Anesthesiologists) ASA physical status I or II, undergoing TEE were enrolled in the study. Exclusion Criteria: Known allergy or hypersensitive reaction to dexmedetomidine Organ dysfunction, and significant developmental delays or behavior problems Cardiac arrhythmia Known. acyanotic congenital heart disease or children after cardiac interventional procedures for follow-up examination.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1-6 months (Group 1)<br> | Drug: intranasal dexmedetomidine<br>* Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).<br>|
| Active Comparator: 7-12 months (Group 2)<br> | Drug: intranasal dexmedetomidine<br>* Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).<br>|
| Active Comparator: 13-18 months (Group 3)<br> | Drug: intranasal dexmedetomidine<br>* Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).<br>|
| Active Comparator: 19-24 months (Group 4)<br> | Drug: intranasal dexmedetomidine<br>* Phase 1, Children received a bolus of intranasal dexmedetomidine which adjusted by the Dixon up-and-down method for TEE study. The first child received 2.5 mcg/kg of intranasal dexmedetomidine dose (100mcg/ml), and the dose varied by 0.1 mcg/kg according to the up-and-down method Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.25 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The ED50 doses for intranasal dexmedetomidine | Phase 1: The starting dose of dexmedetomidine was 2.5 mcg/kg. These doses varied by 0.1 mcg/kg, according to the up-and-down method 18. If the detected MOAA/S score was >3 within 45 minutes after intranasal administration, or clinically adequate diagnostic-quality images could not be acquired, sedation was considered a failure; and the dexmedetomidine dose was increased by 0.1 mcg/kg in the next patient of the same age group. In contrast, if the detected MOAA/S score was ≤3 and the acquisition of clinically adequate diagnostic-quality images was possible, the sedation was considered successful; and the dexmedetomidine dose was decreased by 0.1 mcg/kg in the next patient o | up to 0.5 hours after transthoracic echocardiography | 
| The ED95 doses for intranasal dexmedetomidine | Phase 2 was a dose-escalation study. After interim analysis of the phase 1 results, four dose levels above the calculated ED50 were defined. Dose spacing was set at 0.3 mcg/kg of intranasal dexmedetomidine consistent with the re-estimated standard deviation (SD). Defined levels were set at about 2.5, 2.75, 3.0, and 3.25 mcg/kg of intranasal dexmedetomidine. Criteria for success and failure were identical to those in phase 1. Successful sedation was defined as a MOAA/S score between 0-3 and allowed the acquisition of clinically adequate diagnostic-quality images, while failure was defined as a MOAA/S score >3 within 45 minutes or clinically adequate diagnostic-quality images could not be acquired | up to 0.5 hours after transthoracic echocardiography | 
| Score of physical movement | Movement score was recorded by sonographers who were blinded to the sedative regimen. No movement Occasional, slight movement Frequent, slight movement Vigorous movement limited to extremities Vigorous movement, including torso and head | up to 0.5 hours after transthoracic echocardiography | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| sedation induction time | Successful sedation was defined as an MOAA/S of between 0 and 3, and sedation induction time was defined as the time from drug administration to the onset of satisfactory sedation | up to 2 hours after drug administration | 
| Wake -up time | Children were classified as awake if the MOAA/S was between 4 and 6. Wake -up time was defined as the time from successful sedation until the time that the child awoke | up to 2 hours after drug administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dose-Response Relationship, Drug