Procedural PainNCT05796232
Pharmacogenetics of Ketamine in Children
An observational study of Procedural Pain, run by IRCCS Burlo Garofolo at 1 site in Italy.
Trial summary
The need to treat the children with painful diagnostic-therapeutic procedures has increased in the last years. There is evidence from a wide scientific literature that drugs available in the setting of procedural sedation and analgesia such as midazolam, fentanyl, nitrous oxide, ketamine and propofol are absolutely… Read more about this study
- Who is it for?
- Ages 1 year to 17 years
- Conditions the study is for
- Procedural Pain
- How many people
- 250 participants
- Where
- 1 siteItaly
- Study dates
- 26 Jun 2020to 15 May 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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 year to 17 years
- All sexes
- No healthy volunteers
- Child
Study population: children between 1 and 17 years of age needing sedation and analgesia for painful procedures
Who may be able to join
- Any child between 1 and 17 years of age needing sedation and analgesia for painful procedures, such as suture laceration, fracture reductions, burn medications, bone marrow aspiration, lumbar puncture, arthrocentesis, colonoscopy and others.
- Use of intravenous ketamine as the sole sedative agent for the procedure.
Who cannot join
- Children needing drugs other that ketamine for sedation, such as fentanyl, propofol, midazolam and dexmedetomidine .
- Children with intellectual disability or with non typical neurodevelopment, such as children with autism.
- Children with a history of allergy or hypersensibility to ketamine.
- Parents limitations in language and understanding informed consent forms and procedures.
Trial locations and contacts
1 site in 1 country.
Gabriele Stocco, MSC contact
Italy1 site, 1 recruiting
- Recruiting
IRCCS Burlo Garofolo
Trieste, 34137
Egidio Barbi, MD, +390403785251, egidio.barbi@burlo.trieste.it
About this study
Official title: Pharmacogenetics of Ketamine in Children Presenting Emesis and Recovery Agitation During Procedural Analgesia and Sedation Outside of the Operating Room
The need to treat the children with painful diagnostic-therapeutic procedures has increased in the last years. There is evidence from a wide scientific literature that drugs available in the setting of procedural sedation and analgesia such as midazolam, fentanyl, nitrous oxide, ketamine and propofol are absolutely safe without a significant incidence of adverse effects, if administered by anaesthesiologists and also trained pediatricians outside the operating room. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that blocks glutamate excitatory effects. Ketamine's molecular mechanism is not restricted to the NMDA receptor. Several studies indicate interactions with a series of receptor systems, including opioid, cholinergic and dopaminergic receptors. Ketamine is a safe and effective drug during procedural analgesia and sedation applied to children outside the operating room. A recent multicenter study, showed that ketamine, without being associated with other analgesic or sedative drugs, is the drug regimen with the lowest risk of adverse effects during this procedures. Even though being safe, ketamine may cause some adverse effects. When ketamine is administered for procedural sedation outside the operating room, adverse effects more frequently recorded are emesis and recovery agitation, each with a prevalence of around 8%. Recovery agitation, defined as any abnormal behavioural response such as any combination of agitation, crying, hallucinations or nightmares after sedation, in some cases (around 1%) may be severe and leads to specific treatment, mainly benzodiazepines. Emesis and recovery agitation are minor adverse events, but both may be very unpleasant for the patient and may play a role in the perception of patients and their parents of the quality of sedation, especially in children who need repeated procedures. Identifying patients, particularly children with chronic illnesses and leukemia, at risk of emesis and recovery agitation may facilitate the choice of different drugs regimens, improving the quality of care. The aim of this study is the identification of genetic and epigenetic biomarkers useful to predict emesis and recovery agitation related to administration of ketamine for procedural sedation and analgesia applied to children and to correlate them with the pharmacokinetic profile.
- Conditions
- Procedural Pain
- Keywords
- Procedural pain, Analgesia, Sedation, Children
- Medical subject headings
- Pain, Procedural, Agnosia
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify genetic variants associated with the development of emesis and recovery agitation after intravenous administration of ketamine
Genotyping will be performed using Illumina Omni 2.5 + exome array. Biomarker identification will be performed considering the genetic contribution of variants focusing on 10 candidate genes relevant for the biotransformation (CYP2B6, CYP2C9, CYP3A4, CYP3A5, CYP2A6) and for pharmacodynamics (genes encoding for the NMDA receptor subunits: GRIN1 e GRIN2A-D) of ketamine, selected on the basis of literature. The independent variable associated with ketamine induced adverse effects will be the presence or not of functional variants in the candidate genes.
Measured: 10 minutes before procedural sedation
Secondary outcomes (5)
To assess the maximum plasmatic concentration (Cmax) after intravenous administration of ketamine
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
Measured: 10 minutes before procedural sedation
To assess the area under the concentration curve from time 0 (AUC 0-last) after intravenous administration of ketamine
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
Measured: 10 minutes before procedural sedation
To assess the plasmatic half-life after intravenous administration of ketamine
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
Measured: 10 minutes before procedural sedation
To assess the plasmatic clearance defined as dose/AUC after intravenous administration of ketamine
Ketamine and its main metabolite norketamine will be quantified in plasma through a method of liquid chromatography / tandem mass spectrometry. The pharmacokinetic parameters will be calculated using WinNonlin software.
Measured: 10 minutes before procedural sedation
To identify exosomal miRNAs linked to the development of emesis and recovery agitation after intravenous administration of ketamine
Neuronal-derived exosomes will be isolated and miRNAs will be sequenced. miRNAs contained in neuronal-derived exosomes and associated with ketamine induced adverse effects will be quantified through next generation sequencing.
Measured: 10 minutes before procedural sedation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2023
- Study start26 Jun 2020
- Primary completion15 May 2024 (estimated)
- Study completion15 May 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Procedural PainStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Other
- Time perspective
- Cross-sectional
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IRCCS Burlo Garofolo
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Egidio Barbi, MD, Study director, IRCCS materno infantile Burlo Garofolo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05796232
- Sponsor's protocol ID
- RC 16/19
- Status last verified
- Mar 2023
- First submitted
- 20 Mar 2023
- Last updated
- 3 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacogenetics of Ketamine in Children Presenting Emesis and Recovery Agitation During Procedural Analgesia and Sedation Outside of the Operating Room
- ClinicalTrials.gov ID
- NCT05796232
- Acronym / sponsor ID
- RC 16/19
- Conditions
- Procedural Pain
- Keywords
- Procedural pain, Analgesia, Sedation, Children
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- IRCCS Burlo GarofoloUniversity, hospital or other
- Study start
- 26 Jun 2020 (actual)
- Primary completion
- 15 May 2024 (estimated)
- Study completion
- 15 May 2024 (estimated)
- First posted
- 3 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The need to treat the children with painful diagnostic-therapeutic procedures has increased in the last years. There is evidence from a wide scientific literature that drugs available in the setting of procedural sedation and analgesia such as midazolam, fentanyl, nitrous oxide, ketamine and propofol are absolutely safe without a significant incidence of adverse effects, if administered by anaesthesiologists and also trained pediatricians outside the operating room. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that blocks glutamate excitatory effects. Ketamine's molecular mechanism is not restricted to the NMDA receptor. Several studies indicate interactions with a series of receptor systems, including opioid, cholinergic and dopaminergic receptors. Ketamine is a safe and effective drug during procedural analgesia and sedation applied to children outside the operating room. A recent multicenter study, showed that ketamine, without being associated with other analgesic or sedative drugs, is the drug regimen with the lowest risk of adverse effects during this procedures. Even though being safe, ketamine may cause some adverse effects. When ketamine is administered for procedural sedation outside the operating room, adverse effects more frequently recorded are emesis and recovery agitation, each with a prevalence of around 8%. Recovery agitation, defined as any abnormal behavioural response such as any combination of agitation, crying, hallucinations or nightmares after sedation, in some cases (around 1%) may be severe and leads to specific treatment, mainly benzodiazepines. Emesis and recovery agitation are minor adverse events, but both may be very unpleasant for the patient and may play a role in the perception of patients and their parents of the quality of sedation, especially in children who need repeated procedures. Identifying patients, particularly children with chronic illnesses and leukemia, at risk of emesis and recovery agitation may facilitate the choice of different drugs regimens, improving the quality of care. The aim of this study is the identification of genetic and epigenetic biomarkers useful to predict emesis and recovery agitation related to administration of ketamine for procedural sedation and analgesia applied to children and to correlate them with the pharmacokinetic profile.
Study design
- Observational model
- Other
- Time perspective
- Cross-sectional
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- children between 1 and 17 years of age needing sedation and analgesia for painful procedures
Key inclusion criteria (2 listed)
- Any child between 1 and 17 years of age needing sedation and analgesia for painful procedures, such as suture laceration, fracture reductions, burn medications, bone marrow aspiration, lumbar puncture, arthrocentesis, colonoscopy and others.
- Use of intravenous ketamine as the sole sedative agent for the procedure.
Key exclusion criteria (4 listed)
- Children needing drugs other that ketamine for sedation, such as fentanyl, propofol, midazolam and dexmedetomidine .
- Children with intellectual disability or with non typical neurodevelopment, such as children with autism.
- Children with a history of allergy or hypersensibility to ketamine.
- Parents limitations in language and understanding informed consent forms and procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To identify genetic variants associated with the development of emesis and recovery agitation after intravenous administration of ketamine
Time frame: 10 minutes before procedural sedation
Genotyping will be performed using Illumina Omni 2.5 + exome array. Biomarker identification will be performed considering the genetic contribution of variants focusing on 10 candidate genes relevant for the biotransformation (CYP2B6, CYP2C9, CYP3A4, CYP3A5, CYP2A6) and for pharmacodynamics (genes encoding for the NMDA receptor subunits: GRIN1 e GRIN2A-D) of ketamine, selected on the basis of literature. The independent variable associated with ketamine induced adverse effects will be the presence or not of functional variants in the candidate genes.
5 secondary outcomes
To assess the maximum plasmatic concentration (Cmax) after intravenous administration of ketamine
Time frame: 10 minutes before procedural sedation
To assess the area under the concentration curve from time 0 (AUC 0-last) after intravenous administration of ketamine
Time frame: 10 minutes before procedural sedation
To assess the plasmatic half-life after intravenous administration of ketamine
Time frame: 10 minutes before procedural sedation
To assess the plasmatic clearance defined as dose/AUC after intravenous administration of ketamine
Time frame: 10 minutes before procedural sedation
To identify exosomal miRNAs linked to the development of emesis and recovery agitation after intravenous administration of ketamine
Time frame: 10 minutes before procedural sedation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2023.
- Individual participant dataSharing planned: Undecided
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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.
Gabriele Stocco, MSC contact
Egidio Barbi, MD study director
IRCCS materno infantile Burlo Garofolo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Procedural Pain, run by IRCCS Burlo Garofolo at 1 site in Italy.
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 2 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 3 Apr 2023. 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 Italy. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Egidio Barbi, MD (+390403785251, egidio.barbi@burlo.trieste.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify genetic variants associated with the development of emesis and recovery agitation after intravenous administration of ketamine (time frame: 10 minutes before procedural sedation). 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 3 Apr 2023.