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

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.

Study Overview

• Status: Completed
• Conditions: Patients for Transthoracic Echocardiography; Unknown Diagnosis
• Intervention / Treatment: Drug: intranasal dexmedetomidine

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 320
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Department of Anesthesiology of Guangzhou Women and Children's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1-6 months (Group 1)	Drug: intranasal dexmedetomidine; 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).
Active Comparator: 7-12 months (Group 2)	Drug: intranasal dexmedetomidine; 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).
Active Comparator: 13-18 months (Group 3)	Drug: intranasal dexmedetomidine; 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).
Active Comparator: 19-24 months (Group 4)	Drug: intranasal dexmedetomidine; 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).

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
heart rate	Bradycardia was defined as a reduction in heart rate more than 20% from the baseline values	up to 3 hours after drug administration
Oxyhemoglobin desaturation	Significant Oxyhemoglobin desaturation was defined as < 90%.	up to 3 hours after drug administration
non-invasive systolic blood pressure	Hypotension was defined as a reduction in systolic blood pressure more than 20% from the baseline values	up to 3 hours after drug administration

Collaborators and Investigators

• Sponsor: Guangzhou Women and Children's Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): August 10, 2019
• Primary Completion (Actual): January 1, 2021
• Study Completion (Actual): May 20, 2022

Study Registration Dates

• First Submitted: May 12, 2016
• First Submitted That Met QC Criteria: May 19, 2016
• First Posted (Estimate): May 23, 2016

Study Record Updates

• Last Update Posted (Actual): October 10, 2022
• Last Update Submitted That Met QC Criteria: October 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Dose-Response Relationship, Drug
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: Wzhang03

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No