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

Children's Hospital of Philadelphia (CHOP)

Status and phase: Terminated; Phase 1

Conditions: Dexmedetomidine; Congenital Heart Disease

Treatments: Drug: Dexmedetomidine

Study type: Interventional

Funder types: Other

Identifiers

NCT03417999

17-014084

Details and patient eligibility

About

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.

Full 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.

Enrollment: 28 patients

Sex: All

Ages: 1 month to 6 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female subjects age ≥1 mo to ≤6 yo.
2. Subjects must have congenital heart disease.
3. American Society of Anesthesiology (ASA) Physical Status 1-3.
4. Subjects scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 3hours.
5. Subjects spontaneously ventilating with a natural airway scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 2 hours.
6. Subjects must have reliable intravascular access from which to draw blood samples.

Exclusion criteria

1. History of allergic reaction or sensitivity to dexmedetomidine.
2. Nasal pathology preventing the administration of drug.
3. Patients that are on maintenance medications that could inhibit or induce the CYP2A6 enzyme.
4. Cardiac conduction abnormalities defined as second or third degree heart block or pacemaker dependence.
5. Bradycardia, defined by age, upon arrival in the preoperative care area.
6. 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.
7. The subject has received dexmedetomidine or clonidine within 1 week of the study date.
8. BMI >30.
9. Patients previously enrolled in this study.
10. Any investigational drug use within 30 days prior to enrollment.
11. Wards will not be eligible.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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28 participants in 2 patient groups

Cohort 1

Experimental group

Description:

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

Treatment:

Drug: Dexmedetomidine

Cohort 2

Experimental group

Description:

* Dexmedetomidine 4 μg/kg * Under general oral endotracheal anesthesia * 7 subjects age \>2 yo and ≤ 6 yo

Treatment:

Drug: Dexmedetomidine