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

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

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.

Study Overview

• Status: Terminated
• Conditions: Congenital Heart Disease; Dexmedetomidine
• Intervention / Treatment: Drug: Dexmedetomidine

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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19106
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 6 years (Child)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; 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; Dose-escalation of atomized intranasal dexmedetomidine; Other Names: Precedex
Experimental: Cohort 2; Dexmedetomidine 4 μg/kg; Under general oral endotracheal anesthesia; 7 subjects age >2 yo and ≤ 6 yo	Drug: Dexmedetomidine; Dose-escalation of atomized intranasal dexmedetomidine; Other Names: Precedex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Samples Obtained Per Subject	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. This is the number of samples obtained per subject.	Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
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 - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
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 - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL	Dose-limiting toxicities (DLT) include bradycardia, hypotension, new intraventricular conduction abnormality or any serious adverse event possibly, probably, or definitely related to intranasal dexmedetomidine administration that occured after the administration of the intranasal dexmedetomidine and through the completion of PK sampling. Bradycardia, hypotension, or new intraventricular conduction abnormalities that occured after the administration of intravenous dexmedetomidine given by the primary anesthesia team as part of usual clinical care were not considered DLTs but were considered an adverse event. Any events that could not be explained by the intervention that the patient was undergoing were assumed to be related to the study drug.	Subjects were monitored for 6 hours after the administration of study drug.

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Kelly L Grogan, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2018
• Primary Completion (Actual): October 12, 2021
• Study Completion (Actual): October 12, 2021

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 30, 2018
• First Posted (Actual): January 31, 2018

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Pediatric; Intranasal; Pharmacokinetic
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Diseases; Heart Defects, Congenital; 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: 17-014084

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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