Clinical trial NCT04471402: Determining the Pharmacogenetic Basis of Non-responsiveness to the Sedative Effects of Dexmedetomidine in Children
Official title: Determining the Pharmacogenetic Basis of Non-responsiveness to the Sedative Effects of Dexmedetomidine in Children
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Pharmacogenetic Study
Procedural Anxiety
Dexmedetomidine
Keywords: Procedural anxiety in children
Pharmacogenetic study
Dexmedetomidine
Sedation
Lead sponsor: Hong Kong Children's Hospital
Sponsor class: OTHER
First posted: 2020-07-15
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Children who require intranasal Precedex at 3 mcg/kg as an anxiolytic premedication for radiological or pre-anaesthesia sedation in Hong Kong Children's Hospital

Brief summary: Intranasal Dexmedetomidine is one of the sedative drugs of choice commonly used as an anxiolytic premedication for children for diagnostic or therapeutic procedures. However, some children do not achieve the level of sedation expected with the usual dose after an expected timeframe, leading to distress and costly time wasted.

In this study, we would try to identify a genetic basis to non-responders of Dexmedetomidine by comparing a chosen gene panel of 250 relevant genes between responders and non-responders to a standardized 3mcg/kg intranasal Dexmedetomidine.

Detailed description: For most children, having to endure a diagnostic or therapeutic procedure in a hospital environment is a frightening and distressing experience, especially if it is accompanied by pain or discomfort. In an attempt to minimise the trauma and to maximise co-operation from the child, administration of a sedative is often requested by either the parent or the proceduralist. Some sedative agents may have the side effect reducing the child's efforts in breathing, causing inadequate oxygen to be delivered to and carbon dioxide removed from the body, a state that can be life threatening if left untreated. Other sedative agents may cause unpleasant sensations such as hallucinations or nausea while still others may have a paradoxical effect of exciting rather than sedating the child. Among the available agents that may be administered without the presence of an attendant anaesthesiologist, dexmedetomidine is an agent of choice with minimal incidence of the aforementioned effects. However, we have observed in a small proportion of children that dexmedetomidine does not see to be able to elicit a sedative response in the expected time and with the usual dose. It is possible that there is a genetic bas to this resistance and it would be of great use to be able to predict the non-responders ahead of time so an appropriate alternative may be selected without a trial and error approach.

In this project, children who would require Precedex as first-line sedation for radiological or pre-anaesthesia sedation are asked to participate by providing a buccal swab sample and have their genome (genetic makeup) characterised by target sequencing. They are standardized into receiving 3mcg/kg intranasal Precedex and are observed every 5 minutes afterwards for their level of sedation. They would be identified as 'fast responder', 'normal responder', 'slow responder' and 'definite non-responder'.

A gene panel of 250 relevant genes is chosen and compared between the different groups of responders and non-responders. We will then try to look for the differences between these groups and we will use this information to build a predictive model. This model will help to identify non-responders in the future and this would allow clinicians to prepare for an alternative approach to sedation. This would save time, distress to the child and parent and ultimately cost to the institution.

Eligibility criteria: Inclusion Criteria:

* Children who would receive 3mcg/kg intranasal Precedex as a first line sedative agent for radiological procedures or for pre-anaesthesia sedation
* Written informed consent from parent or legal guardian

Exclusion Criteria:

* Known allergy or hypersensitivity to Precedex
* Pre-existing developmental delay
* Neurological impairment
* Autism
* Fever (temperature \>/= 38.5c)
* Major organ dysfunction
* Cardiac arrhythmia
* Cardiac failure
* Subjects who would require a dose exceeding 100mcg if 3mcg/kg dose is achieved
* Subjects who have failed intranasal administration of Dexmedetomidine

Primary outcomes:
measure: Sedative response to intranasal Precedex
timeFrame: Every 5 minutes till 30 minutes from administration of intranasal Precedex
Secondary outcomes:
measure: Onset time of sedation
timeFrame: 45 minutes from administration of intranasal Precedex
measure: Incidence of bradycardia
timeFrame: 2 hour from administration of intranasal Precedex or until administration of other sedative or anaesthetic drugs, whichever is shorter
measure: Incidence of hypotension
timeFrame: 2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter
measure: Incidence of hypertension
timeFrame: 2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter
measure: Incidence of hypoxia
timeFrame: 2 hours from administration of intranasal Precedex, or until administration of other sedative or anaesthetic drugs, whichever is shorter
measure: Wake up time
timeFrame: 1 hour after completion of procedure
measure: Length of procedure
timeFrame: 3 hours
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Hong Kong Children's Hospital
Study officials:
affiliation: Hong Kong Children's Hospital
name: Vivian MY Yuen, M.D.
role: PRINCIPAL_INVESTIGATOR
References: