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Pharmacokinetic Study of Dexmedetomidine After Intra-nasal Dosing in Children

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02836431
Recruitment Status : Completed
First Posted : July 19, 2016
Last Update Posted : July 30, 2018
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief 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.

Condition or disease Intervention/treatment Phase
Heart Disease Drug: Dexmedetomidine 1mcg/kg Intranasal Drug: Dexmedetomidine 2mcg/kg Intranasal Drug: Dexmedetomidine 1mcg Intravenous Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Pharmacokinetic Study of Dexmedetomidine After Intra-nasal Dosing in Children
Study Start Date : January 2016
Actual Primary Completion Date : December 2017
Actual Study Completion Date : April 2018

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Maximum blood concentration level of DEX - Cmax [ Time Frame: Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours ]
    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.

  2. The amount of time that a DEX is present at the maximum concentration - Tmax [ Time Frame: Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours ]
    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.

  3. Area under the curve for DEX concentration levels [ Time Frame: Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours ]
    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.

  4. Bioavailability of intranasal DEX relative to intravenous DEX for distribution - plasma concentration [ Time Frame: Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours ]
    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.

  5. Bioavailability of intranasal DEX relative to intravenous DEX for elimination - plasma concentration [ Time Frame: Blood samples will be drawn until immediately prior to Cardiopulmonary bypass, an expected average of 2 hours ]
    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.


Secondary Outcome Measures :
  1. Adverse events associated with DEX administration [ Time Frame: Participants will be followed until cardiopulmonary bypass, an expected duration of 2 hours. ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 48 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02836431


Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Jeff Miller, MD Children's Hospital Medical Center, Cincinnati
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02836431    
Other Study ID Numbers: 2015-5966
First Posted: July 19, 2016    Key Record Dates
Last Update Posted: July 30, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Pediatric
Sedation
Dexmedetomidine
Additional relevant MeSH terms:
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Heart Diseases
Cardiovascular Diseases
Dexmedetomidine
Hypnotics and Sedatives
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action