DexmedetomidinePhase 1NCT03417999
Pharmacokinetic Study of Intranasal Dexmedetomidine in Pediatric Patients With Congenital Heart Disease
A Phase 1 study testing Dexmedetomidine in people with Dexmedetomidine and Congenital Heart Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 6 years
- Conditions the study is for
- Dexmedetomidine, Congenital Heart Disease
- What is being tested?
- Dexmedetomidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jun 2018to 12 Oct 2021
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female subjects age ≥1 mo to ≤6 yo.
- Subjects must have congenital heart disease.
- American Society of Anesthesiology (ASA) Physical Status 1-3.
- Subjects scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 3hours.
- Subjects spontaneously ventilating with a natural airway scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 2 hours.
- Subjects must have reliable intravascular access from which to draw blood samples.
Who cannot join
- History of allergic reaction or sensitivity to dexmedetomidine.
- Nasal pathology preventing the administration of drug.
- Patients that are on maintenance medications that could inhibit or induce the CYP2A6 enzyme.
- Cardiac conduction abnormalities defined as second or third degree heart block or pacemaker dependence.
- Bradycardia, defined by age, upon arrival in the preoperative care area.
- 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.
Show all 11Show fewer
- The subject has received dexmedetomidine or clonidine within 1 week of the study date.
- BMI >30.
- Patients previously enrolled in this study.
- Any investigational drug use within 30 days prior to enrollment.
- Wards will not be eligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19106
About this study
Official title: 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.
Read the 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
- Being tested
- Dexmedetomidine
- Keywords
- Intranasal, Pharmacokinetic, Pediatric
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexmedetomidineDrug
Also called Precedex
Dose-escalation of atomized intranasal dexmedetomidine
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | 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 Receives: Drug: Dexmedetomidine |
| Cohort 2 | Experimental | * Dexmedetomidine 4 μg/kg
* Under general oral endotracheal anesthesia
* 7 subjects age >2 yo and ≤ 6 yo Receives: Drug: Dexmedetomidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Subjects were monitored for 6 hours after the administration of study drug.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2018
- Study start14 Jun 2018
- Primary completion12 Oct 2021
- Study completion12 Oct 2021
Why it stopped: All subjects who were enrolled completed the study. However, the PI left the institution and the study was terminated before all cohorts were enrolled.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DexmedetomidineStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kelly Grogan, Children's Hospital of Philadelphia
- Investigators
- Kelly L Grogan, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03417999
- Sponsor's protocol ID
- 17-014084
- Status last verified
- Sep 2023
- First submitted
- 8 Jan 2018
- Last updated
- 22 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Escalation Pharmacokinetic Study of Intranasal Atomized Dexmedetomidine in Pediatric Patients With Congenital Heart Disease
- ClinicalTrials.gov ID
- NCT03417999
- Acronym / sponsor ID
- 17-014084
- Conditions
- Dexmedetomidine, Congenital Heart Disease
- Keywords
- Intranasal, Pharmacokinetic, Pediatric
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: All subjects who were enrolled completed the study. However, the PI left the institution and the study was terminated before all cohorts were enrolled.
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- 14 Jun 2018 (actual)
- Primary completion
- 12 Oct 2021 (actual)
- Study completion
- 12 Oct 2021 (actual)
- First posted
- 31 Jan 2018 (actual)
- Results
- Posted 22 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: DexmedetomidineCohort 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 |
| Cohort 2 | Experimental | Drug: Dexmedetomidine* Dexmedetomidine 4 μg/kg * Under general oral endotracheal anesthesia * 7 subjects age >2 yo and ≤ 6 yo |
Who may qualify
- Ages
- 1 month to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Male or female subjects age ≥1 mo to ≤6 yo.
- Subjects must have congenital heart disease.
- American Society of Anesthesiology (ASA) Physical Status 1-3.
- Subjects scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 3hours.
- Subjects spontaneously ventilating with a natural airway scheduled for elective cardiac interventional or diagnostic catheterization anticipated to last ≥ 2 hours.
Key exclusion criteria (11 listed)
- History of allergic reaction or sensitivity to dexmedetomidine.
- Nasal pathology preventing the administration of drug.
- Patients that are on maintenance medications that could inhibit or induce the CYP2A6 enzyme.
- Cardiac conduction abnormalities defined as second or third degree heart block or pacemaker dependence.
- Bradycardia, defined by age, upon arrival in the preoperative care area.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexmedetomidineAlso: PrecedexDose-escalation of atomized intranasal dexmedetomidine | Drug | Cohort 1, Cohort 2 |
Primary outcome
Number of Samples Obtained Per Subject
Time frame: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
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.
Time of Peak Drug Concentration Level of Dexmedetomidine
Time frame: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
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.
Serum Drug Concentration Levels of Dexmedetomidine
Time frame: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration
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.
Dose-limiting Toxicities (DLT) and/or Maximum Plasma Level > 1000 pg/mL
Time frame: Subjects were monitored for 6 hours after the administration of study drug.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kelly L Grogan, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dexmedetomidine in people with Dexmedetomidine and Congenital Heart Disease, run by Children's Hospital of Philadelphia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 22 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Samples Obtained Per Subject (time frame: Up to 5 hours - 0, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, and 300 minutes post drug administration). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Mar 2024.