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

• ClinicalTrials.gov Identifier: NCT02780427
• Recruitment Status: Recruiting
• First Posted: May 23, 2016
• Last Update Posted: August 2, 2019
• Sponsor: Guangzhou Women and Children's Medical Center
• Information provided by (Responsible Party): Wenhua Zhang, Guangzhou Women and Children's Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Patients for Transthoracic Echocardiography; Unknown Diagnosis	Drug: intranasal dexmedetomidine	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 320 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: ED50 and ED95 of Intranasal Dexmedetomidine in Pediatric Patients Undergoing Transthoracic Echocardiography Study
• Estimated Study Start Date: December 2019
• Estimated Primary Completion Date: December 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. The ED50 doses for intranasal dexmedetomidine [ Time Frame: up to 0.5 hours after transthoracic echocardiography ]
   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
2. The ED95 doses for intranasal dexmedetomidine [ Time Frame: up to 0.5 hours after transthoracic echocardiography ]

   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

3. Score of physical movement [ Time Frame: up to 0.5 hours after transthoracic echocardiography ]

   Movement score was recorded by sonographers who were blinded to the sedative regimen.

   1. No movement
   2. Occasional, slight movement
   3. Frequent, slight movement
   4. Vigorous movement limited to extremities
   5. Vigorous movement, including torso and head

Secondary Outcome Measures :

1. sedation induction time [ Time Frame: up to 2 hours after drug administration ]
   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
2. Wake -up time [ Time Frame: up to 2 hours after drug administration ]
   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

Other Outcome Measures:

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

Eligibility Criteria

• Ages Eligible for Study: 1 Month to 24 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Wenhua Zhang, MD; +8613611453199; zhangcobra@126.com

Contact: Yanting Fang, MD; +8618198907630; 13560358327@163.com

Locations

China, Guangdong

Department of Anesthesiology of Guangzhou Women and Children's Medical Center; Recruiting

Guangzhou, Guangdong, China, 510000

Contact: Wenhua Zhang, MD 8613611453199 zhangcobra@126.com

Contact: Yanting Fan, MD 8613560358372 849412396@qq.com

Sponsors and Collaborators

Guangzhou Women and Children's Medical Center

More Information

• Responsible Party: Wenhua Zhang, Director, Clinical Resesearch, Guangzhou Women and Children's Medical Center
• ClinicalTrials.gov Identifier: NCT02780427
• Other Study ID Numbers: Wzhang03
• First Posted: May 23, 2016
• Last Update Posted: August 2, 2019
• Last Verified: August 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wenhua Zhang, Guangzhou Women and Children's Medical Center:

Dose-Response Relationship, Drug

Additional relevant MeSH terms:

Dexmedetomidine; Hypnotics and Sedatives; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action