Pharmacokinetic Study of Intranasal Dexmedetomidine in Pediatric Patients With Congenital Heart Disease

Study Overview
=================
Brief Summary
-----------------
The main objectives of the study are to determine peak plasma drug concentration levels and corresponding time of dexmedetomidine following intranasal administration in children age ≥1 mo to ≤ 6 yr with congenital heart disease undergoing an elective diagnostic or interventional cardiac catheterization procedure.

Detailed Description
-----------------
The high anxiety levels that children may experience during the preoperative period may be associated with negative medical, psychological, and social consequences. To reduce this stress, and to facilitate separation from parents and the induction of anesthesia, children are often given a sedative prior to undergoing a procedure. Dexmedetomidine is a highly selective a2-adrenergic receptor agonist with sedative, anxiolytic, and analgesic properties. While off-label in its use, the administration of dexmedetomidine by the intranasal route has become a popular and effective technique for sedation in children because it is non-invasive, easy to administer, well tolerated, and relatively fast in onset. Despite this, little consistent data have been published on its onset time, duration of action, or optimal dose. The only available pharmacokinetic (PK) data on dexmedetomidine in pediatric patients is in children who were administered IV dexmedetomidine. We are proposing a prospective open-label inter-subject cohort dose-escalation pharmacokinetic study to obtain peak dexmedetomidine drug concentration level in plasma and the corresponding time point following intranasal administration in the pediatric patient with cardiac disease.

Official Title
-----------------
Dose Escalation Pharmacokinetic Study of Intranasal Atomized Dexmedetomidine in Pediatric Patients With Congenital Heart Disease

Conditions
-----------------
Dexmedetomidine, Congenital Heart Disease

Intervention / Treatment
-----------------
* Drug: Dexmedetomidine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects age ≥1 mo to ≤6 yo. Subjects must have congenital heart disease. American Society of Anesthesiology (ASA) Physical Status 1-3. Subjects scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 3hours. Subjects spontaneously ventilating with a natural airway scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 2 hours. Subjects must have reliable intravascular access from which to draw blood samples. Exclusion Criteria: History of allergic reaction or sensitivity to dexmedetomidine. Nasal pathology preventing the administration of drug. Patients that are on maintenance medications that could inhibit or induce the CYP2A6 enzyme. Cardiac conduction abnormalities defined as second or third degree heart block or pacemaker dependence. Bradycardia, defined by age, upon arrival in the preoperative care area. Hepatic dysfunction defined as a history of hepatic dysfunction AND an Alanine Aminotransferase (ALT) value greater than 2 times normal in the 6 months prior to study drug administration. The subject has received dexmedetomidine or clonidine within 1 week of the study date. BMI >30. Patients previously enrolled in this study. Any investigational drug use within 30 days prior to enrollment. Wards will not be eligible.

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 6 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Cohort 1A: Dexmedetomidine 2 μg/kg Under general oral endotracheal anesthesia 7 subjects age >2 yo and ≤ 6 yo 7 subjects age ≥1 mo and ≤2 yo Cohort 1B: Dexmedetomidine 2 μg/kg Under sedation with a natural airway 7 subjects age >2 yo and ≤ 6 yo 7 subjects age ≥1 mo and ≤2 yo | Drug: Dexmedetomidine<br>* Dose-escalation of atomized intranasal dexmedetomidine<br>* Other names: Precedex;|
| Experimental: Cohort 2<br>Dexmedetomidine 4 μg/kg Under general oral endotracheal anesthesia 7 subjects age >2 yo and ≤ 6 yo | Drug: Dexmedetomidine<br>* Dose-escalation of atomized intranasal dexmedetomidine<br>* Other names: Precedex;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum drug concentration levels of dexmedetomidine | Following administration of atomized intranasal dexmedetomidine, serum samples will be obtained at the following times post administrations: 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes. Peak concentration will be determined based on this data. | Up to 5 hours | 
| Time of peak drug concentration level of dexmedetomidine | Following the administration of atomized intranasal dexmedetomidine, serum samples will be drawn at 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240 and 300 minutes post drug administration. The time of peak drug concentration will be determined based on this data. | Up to 5 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Intranasal, Pharmacokinetic, Pediatric