Clinical trial NCT03417999: Pharmacokinetic Study of Intranasal Dexmedetomidine in Pediatric Patients With Congenital Heart Disease
Official title: Dose Escalation Pharmacokinetic Study of Intranasal Atomized Dexmedetomidine in Pediatric Patients With Congenital Heart Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Dexmedetomidine
Congenital Heart Disease
Keywords: Intranasal
Pharmacokinetic
Pediatric
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
First posted: 2018-01-31
Enrollment: 28
Sex: ALL
Minimum age (years): 1
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: OTHER

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Samples Obtained Per Subject
timeFrame: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
measure: Time of Peak Drug Concentration Level of Dexmedetomidine
timeFrame: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
measure: Serum Drug Concentration Levels of Dexmedetomidine
timeFrame: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
measure: Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL
timeFrame: Subjects were monitored for 6 hours after the administration of study drug.
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Kelly L Grogan, MD
role: PRINCIPAL_INVESTIGATOR
References: