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

NCT ID: NCT03417999

Last Updated: 2024-03-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-14
• Study Completion Date: 2021-10-12

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.

Conditions

Dexmedetomidine; Congenital Heart Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Dose-escalation of atomized intranasal dexmedetomidine

Cohort 2

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

Group Type: EXPERIMENTAL

Dexmedetomidine

Intervention Type: DRUG

Dose-escalation of atomized intranasal dexmedetomidine

Interventions

Dexmedetomidine

Dose-escalation of atomized intranasal dexmedetomidine

Intervention Type: DRUG

Other Intervention Names

Precedex

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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Kelly Grogan

Attending Physician, Anesthesia and Critical Care Medicine, Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kelly L Grogan, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

17-014084

Identifier Type: -

Identifier Source: org_study_id