Pharmacokinetic Study of Dexmedetomidine After Intra-nasal Dosing in Children

Heart Disease Clinical Trial

Official title:

Pharmacokinetic Study of Dexmedetomidine After Intra-nasal Dosing in Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02836431
• Other study ID #: 2015-5966
• Status: Completed
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: April 2018

Study information

• Verified date: July 2018
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is examining the absorption of the sedative dexmedetomidine (DEX) in the blood when given by nasal spray. The study will help us determine the best dosing amount for children undergoing sedation or anesthesia with DEX.

Description:

The study will be a prospective study of plasma concentrations after intranasal (1 µg/kg and 2µg/kg) and intravenous (1 µg /kg) DEX to determine the early pharmacokinetics (maximum concentration (peak) and time to peak) and bioavailability of a single intranasal dose in pediatric patients.

Dexmedetomidine sedation is commonly utilized at Cincinnati Children's Medical Center (CCHMC) and other pediatric institutions. This compound is delivered intravenously or intranasally for sedation in children with and without congenital heart disease. Intranasal DEX, though very effective for sedation, has significant variability in its onset and peak effect. Patient care will be significantly improved if factors that determine this variability in onset and peak effect can be determined. Investigators will determine the important early clinical variables of peak plasma DEX concentration (Tmax and Cmax) and the 0 - 2 hour bioavailability of intranasal DEX in children.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: April 2018
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 48 Months

Eligibility

Inclusion Criteria:

• Children aged 6 - 48 months (inclusive) scheduled to receive anesthesia for elective cardiac surgery.

• The subject must be a candidate to receive DEX. A physician member of the Division of Cardiac Anesthesiology, not involved in the study, will make this decision.

• The subject's legally authorized representative has given written informed consent to participate in the study.

Exclusion Criteria:

• Post-natal age (PNA) < 6 months

• The subject is allergic to or has a contraindication to DEX

• Severely depressed ventricular function (ejection fraction 30% or less) on preoperative echocardiogram

• The subject has high risk cardiac conduction system disease at the discretion of the attending anesthesiologist or cardiologist.

• The subject has a hemodynamically significant coarctation or other left heart outflow obstruction

• The subject has received digoxin, beta-adrenergic antagonist, or calcium-channel antagonist on the day of the study

• The subject has received DEX within 1 week of the study date (information obtained from: parent or Medical record)

• Subject have nasal/respiratory symptoms which in the opinion of the Principal investigator, may affect intranasal drug absorption.

Related Conditions & MeSH terms

• Heart Disease
• Heart Diseases

Intervention

Drug:
• Dexmedetomidine 1mcg/kg Intranasal
DEX 1 mcg/kg Intranasal
• Dexmedetomidine 2mcg/kg Intranasal
DEX 2 mcg/kg Intranasal
• Dexmedetomidine 1mcg Intravenous
DEX 1 mcg/kg Intravenously

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum blood concentration level of DEX - Cmax	DEX concentration will be measured in the blood to determine the time point with the maximum concentration (Cmax). Blood samples will be obtained at baseline, and 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, and 2 hours after receiving DEX. If cardiopulmonary bypass (CPB) is delayed beyond two hours, one final blood sample will be obtained immediately prior to CPB.	Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours
Primary	The amount of time that a DEX is present at the maximum concentration - Tmax	DEX concentration will be measured in the blood to determine the time point with the maximum concentration and how long that maximum concentration lasts (Tmax). Blood samples will be obtained at baseline, and 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, and 2 hours after receiving DEX. If cardiopulmonary bypass (CPB) is delayed beyond two hours, one final blood sample will be obtained immediately prior to CPB.	Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours
Primary	Area under the curve for DEX concentration levels	DEX concentration will be measured in the blood samples. Blood samples will be obtained at baseline, and 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, and 2 hours after receiving DEX. If cardiopulmonary bypass (CPB) is delayed beyond two hours, one final blood sample will be obtained immediately prior to CPB.	Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours
Primary	Bioavailability of intranasal DEX relative to intravenous DEX for distribution - plasma concentration	Data will also be analyzed using population modeling using nonlinear mixed effect modeling (NONMEM). Investigators are limited in sampling duration to the onset time for cardiopulmonary bypass in this patient population (approximately two hours), investigators will be measuring distribution for approximately one half-life of DEX. This will allow us to estimate the important clinical parameter of relative 0-2h bioavailability of intranasal vs intravenous DEX.	Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours
Primary	Bioavailability of intranasal DEX relative to intravenous DEX for elimination - plasma concentration	Data will also be analyzed using population modeling using nonlinear mixed effect modeling (NONMEM). Investigators are limited in sampling duration to the onset time for cardiopulmonary bypass in this patient population (approximately two hours), investigators will be measuring elimination for approximately one half-life of DEX. This will allow us to estimate the important clinical parameter of relative 0-2h bioavailability of intranasal vs intravenous DEX.	Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours
Secondary	Adverse events associated with DEX administration	Heart rate and blood pressure are recorded by clinical staff prior to the procedure and continuously during the procedure. The heart rate and blood pressure during the time of study blood collection will be compared to the baseline vitals to determine if any adverse events occurred.	Participants will be followed until cardiopulmonary bypass, an expected duration of 2 hours.