Pharmacokinetic Study of Dexmedetomidine After Intra-nasal Dosing in Children

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.

Study Overview

• Status: Completed
• Conditions: Heart Disease
• Intervention / Treatment: Drug: Dexmedetomidine 1mcg/kg Intranasal; Drug: Dexmedetomidine 2mcg/kg Intranasal; Drug: Dexmedetomidine 1mcg Intravenous

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 months to 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DEX 1 mcg/kg Intranasal; Standard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia , placement of an endotracheal tube and an arterial line. Once these are accomplished, dexmedetomidine is administered according to group assignment.	Drug: Dexmedetomidine 1mcg/kg Intranasal; DEX 1 mcg/kg Intranasal
Experimental: DEX 2 mcg/kg Intranasal; Standard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia , placement of an endotracheal tube and an arterial line. Once these are accomplished, dexmedetomidine is administered according to group assignment.	Drug: Dexmedetomidine 2mcg/kg Intranasal; DEX 2 mcg/kg Intranasal
Experimental: DEX 1 mcg/kg Intravenous; Standard anesthesia care for a patient presenting for cardiac surgery includes induction of general anesthesia , placement of an endotracheal tube and an arterial line. Once these are accomplished, dexmedetomidine is administered according to group assignment.	Drug: Dexmedetomidine 1mcg Intravenous; DEX 1 mcg/kg Intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Investigators: Principal Investigator: Jeff Miller, MD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start: January 1, 2016
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): April 1, 2018

Study Registration Dates

• First Submitted: January 8, 2016
• First Submitted That Met QC Criteria: July 14, 2016
• First Posted (Estimate): July 19, 2016

Study Record Updates

• Last Update Posted (Actual): July 30, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Pediatric; Sedation; Dexmedetomidine
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; 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: 2015-5966

Plan for Individual participant data (IPD)

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