AnesthesiaPhase 4NCT04164264
Genetic Differences in Propofol Pharmacodynamics in Children
A Phase 4 study testing Propofol in people with Anesthesia, run by University of British Columbia at 1 site in Canada.
Trial summary
Propofol is an extensively utilized intravenous sedative and general anesthetic. However, propofol has a narrow therapeutic index, and this means that there is only a small difference in the dose required to produce loss of consciousness and the dose required to produce potentially life-threatening effects such as… Read more about this study
- Who is it for?
- Ages 3 to 18 years
- Conditions the study is for
- Anesthesia
- What is being tested?
- Propofol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 360 participants
- Where
- 1 siteCanada
- Study dates
- 11 Mar 2020to Dec 2024
- Phase
- Phase 4
- 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 3 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 3 to ≤ 18
- ASA physical status classification I-III
- Intravenous induction resulting in apnea clinically appropriate and indicated
Who cannot join
- Age < 3 or >18
- ASA physical status IV-V
- Propofol induction to apnea not indicated or feasible
- Sedative premedication
- Severe neurological impairment, expected to reduce propofol requirement as judged by the clinical experience of the anaesthetist
- Weight <3%ile or >97%ile for age
Trial locations and contacts
1 site in 1 country.
Canada1 site
BC Children's Hospital - Department of Anesthesia
Vancouver, British Columbia, V6H 3V4
About this study
Official title: Genetic Differences in Pharmacodynamic Safety Endpoints With Propofol Anaesthesia in Children
Propofol is an extensively utilized intravenous sedative and general anesthetic. However, propofol has a narrow therapeutic index, and this means that there is only a small difference in the dose required to produce loss of consciousness and the dose required to produce potentially life-threatening effects such as loss of protective airway reflexes and cessation of spontaneous breathing. Moreover, there is substantial variation between individuals in the doses required to achieve these pharmacodynamic endpoints.
Given the inexorable rise in demand for pediatric sedation and the increasing use of propofol in sedation protocols by non-anaesthesiologists, the purpose of this study is to refine the propofol dosing recommendations to account for pharmacogenomic variability to make procedural sedation safer for children. Experienced users already adjust for age and body weight. This study may enable further refinements according to sex and - novelly - ancestry.
Read the detailed description
Hypothesis:
The investigators hypothesize that examination of genome-wide association study (GWAS) findings will enable the investigators to provide pharmacogenomic insights into clinically observed - and, with this study, quantified - differences in propofol requirements for loss of consciousness (LOC) and apnea in children. It is further hypothesized that the distribution of allelic variants in these pharmacogenes may differ between children of different genomic ancestry.
Objectives:
Primary: (i) To describe and quantify doses of propofol required to produce loss of consciousness and apnea in children of differing ages, sex and self-identified countries of origin. (ii) To identify genomic associations that may explain variability, and generate hypotheses for further study. (iii) To identify genomic ancestry and examine how pharmacogene allele variants that may explain the findings of (i) above are distributed across genomic ancestries.
Secondary: To examine the correlation between self-identified countries of family origin and genomic ancestry.
Methods:
Prospective, non-randomized, single cohort study of two pharmacodynamic endpoints (loss of consciousness and apnea), in children requiring propofol anesthesia, with subsequent genome-wide association study (GWAS) and principal component analysis (PCA) to examine, respectively, pharmacogenomic explanations for pharmacodynamic variability and genomic ancestry.
- Conditions
- Anesthesia
- Being tested
- Propofol
- Keywords
- Propofol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
Also called Propofol Injection 1%
At T0, a propofol infusion at a rate of 1.5 mg/kg/min will be started until apnea is achieved. Loss of consciousness will be defined clinically using loss of eyelash reflex (TLOER) and tolerance of nasal cannulae (TNC), tested every 10 sec., and by a BIS <60 for 30 sec. (TBIS). Apnea will be defined as absence of end-tidal CO2 for at least 20 seconds (TAPNEA). A saliva sample with be taken under anesthesia for genome-wide association study and principal component analysis.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous Propofol Infusion | Experimental | Quantification of the dose of propofol required to produce loss of consciousness and apnea. Receives: Drug: Propofol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose of propofol required to produce loss of consciousness
Loss of consciousness will be defined clinically when there is a loss of eyelash reflex, a tolerance of nasal cannulae, and when the Bispectral Index <60 for 30 sec.
Measured: Loss of consciousness will be expected to occur somewhere between 120-180 seconds after commencing the induction infusion.
Dose of propofol required to produce apnea
Apnea will be defined as absence of end-tidal CO2 for at least 20 seconds.
Measured: Apnea will be expected to occur within 10 min after commencing the induction infusion.
Secondary outcomes (2)
Self-identified countries of family origin up to grandparents
The participant will report the countries which make up the participant's ancestral background, up to the country of origin of the grandparents.
Measured: Within 10 minutes after consent to participate.
A genotyped/imputed dataset of 8 million genetic variants aggregated using SHAPEIT (v2), IMPUTE2 (v2.3.2), Phase 3 1000 Genomes Project reference panel, SNP2HLA (v1.0.2), and the Type 1 Diabetes Genetics Consortium reference panel.
Extensive genome-wide genotyping to determine genetic variants of the pathways involved in propofol biotransformation. The array captures both common and rare variation collected from large-scale sequencing projects.
Measured: Saliva sample collected immediately after apnea, within 10min of propofol infusion start. Genomic analysis will be performed post-hoc.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2019
- Study start11 Mar 2020
- Primary completion26 Oct 2023
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AnesthesiaStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe 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 4
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 360 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Collaborators
- BC Children's Hospital Research Institute
- Responsible party
- Principal investigator, Simon Whyte, University of British Columbia
- Investigators
- Simon Whyte, MBBS, FRCA, Principal investigator, BC Children's Hospital, Department of Anesthesia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04164264
- Sponsor's protocol ID
- H19-00188
- Status last verified
- Apr 2024
- First submitted
- 6 Nov 2019
- Last updated
- 22 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Moxham L, Golam A, West NC, Gorges M, Whyte SD. Pharmacodynamic Safety Endpoints for Propofol Anesthesia in Children by Age and Sex: A Multicohort Observational Study. Paediatr Anaesth. 2025 Dec;35(12):1071-1079. doi: 10.1111/pan.70031. Epub 2025 Aug 11.
PubMed 40788031
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Differences in Pharmacodynamic Safety Endpoints With Propofol Anaesthesia in Children
- ClinicalTrials.gov ID
- NCT04164264
- Acronym / sponsor ID
- H19-00188
- Conditions
- Anesthesia
- Keywords
- Propofol
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 360 participants (actual)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Collaborators
- BC Children's Hospital Research Institute
- Study start
- 11 Mar 2020 (actual)
- Primary completion
- 26 Oct 2023 (actual)
- Study completion
- Dec 2024 (estimated)
- First posted
- 15 Nov 2019 (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.
Propofol is an extensively utilized intravenous sedative and general anesthetic. However, propofol has a narrow therapeutic index, and this means that there is only a small difference in the dose required to produce loss of consciousness and the dose required to produce potentially life-threatening effects such as loss of protective airway reflexes and cessation of spontaneous breathing. Moreover, there is substantial variation between individuals in the doses required to achieve these pharmacodynamic endpoints.
Given the inexorable rise in demand for pediatric sedation and the increasing use of propofol in sedation protocols by non-anaesthesiologists, the purpose of this study is to refine the propofol dosing recommendations to account for pharmacogenomic variability to make procedural sedation safer for children. Experienced users already adjust for age and body weight. This study may enable further refinements according to sex and - novelly - ancestry.
Detailed description
Hypothesis:
The investigators hypothesize that examination of genome-wide association study (GWAS) findings will enable the investigators to provide pharmacogenomic insights into clinically observed - and, with this study, quantified - differences in propofol requirements for loss of consciousness (LOC) and apnea in children. It is further hypothesized that the distribution of allelic variants in these pharmacogenes may differ between children of different genomic ancestry.
Objectives:
Primary: (i) To describe and quantify doses of propofol required to produce loss of consciousness and apnea in children of differing ages, sex and self-identified countries of origin. (ii) To identify genomic associations that may explain variability, and generate hypotheses for further study. (iii) To identify genomic ancestry and examine how pharmacogene allele variants that may explain the findings of (i) above are distributed across genomic ancestries.
Secondary: To examine the correlation between self-identified countries of family origin and genomic ancestry.
Methods:
Prospective, non-randomized, single cohort study of two pharmacodynamic endpoints (loss of consciousness and apnea), in children requiring propofol anesthesia, with subsequent genome-wide association study (GWAS) and principal component analysis (PCA) to examine, respectively, pharmacogenomic explanations for pharmacodynamic variability and genomic ancestry.
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intravenous Propofol Infusion | Experimental | Drug: PropofolQuantification of the dose of propofol required to produce loss of consciousness and apnea. |
Who may qualify
- Ages
- 3 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- Age ≥ 3 to ≤ 18
- ASA physical status classification I-III
- Intravenous induction resulting in apnea clinically appropriate and indicated
Key exclusion criteria (6 listed)
- Age < 3 or >18
- ASA physical status IV-V
- Propofol induction to apnea not indicated or feasible
- Sedative premedication
- Severe neurological impairment, expected to reduce propofol requirement as judged by the clinical experience of the anaesthetist
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 |
|---|---|---|
| PropofolAlso: Propofol Injection 1%At T0, a propofol infusion at a rate of 1.5 mg/kg/min will be started until apnea is achieved. Loss of consciousness will be defined clinically using loss of eyelash reflex (TLOER) and tolerance of nasal cannulae (TNC), tested every 10 sec., and by a BIS <60 for 30 sec. (TBIS). Apnea will be defined as absence of end-tidal CO2 for at least 20 seconds (TAPNEA). A saliva sample with be taken under anesthesia for genome-wide association study and principal component analysis. | Drug | Intravenous Propofol Infusion |
Primary outcome
Dose of propofol required to produce loss of consciousness
Time frame: Loss of consciousness will be expected to occur somewhere between 120-180 seconds after commencing the induction infusion.
Loss of consciousness will be defined clinically when there is a loss of eyelash reflex, a tolerance of nasal cannulae, and when the Bispectral Index <60 for 30 sec.
Dose of propofol required to produce apnea
Time frame: Apnea will be expected to occur within 10 min after commencing the induction infusion.
Apnea will be defined as absence of end-tidal CO2 for at least 20 seconds.
2 secondary outcomes
Self-identified countries of family origin up to grandparents
Time frame: Within 10 minutes after consent to participate.
A genotyped/imputed dataset of 8 million genetic variants aggregated using SHAPEIT (v2), IMPUTE2 (v2.3.2), Phase 3 1000 Genomes Project reference panel, SNP2HLA (v1.0.2), and the Type 1 Diabetes Genetics Consortium reference panel.
Time frame: Saliva sample collected immediately after apnea, within 10min of propofol infusion start. Genomic analysis will be performed post-hoc.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Derived from this study: PubMed 40788031Moxham L, Golam A, West NC, Gorges M, Whyte SD. Pharmacodynamic Safety Endpoints for Propofol Anesthesia in Children by Age and Sex: A Multicohort Observational Study. Paediatr Anaesth. 2025 Dec;35(12):1071-1079. doi: 10.1111/pan.70031. Epub 2025 Aug 11.
- Pediatric Anesthesia Research Team websiteLink provided by the sponsor.
- 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.
Simon Whyte, MBBS, FRCA principal investigator
BC Children's Hospital, Department of Anesthesia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Propofol in people with Anesthesia, run by University of British Columbia at 1 site in Canada.
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 3 inclusion and 6 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 22 Apr 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 Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
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?
Dose of propofol required to produce loss of consciousness (time frame: Loss of consciousness will be expected to occur somewhere between 120-180 seconds after commencing the induction infusion.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04164264, which also lists 1 linked publication.
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 Apr 2024.