Genetic Differences in Propofol Pharmacodynamics in Children

Status Active, not recruiting

Clinical 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 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.

Clinical Trial 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

Related Conditions & MeSH terms

Anesthesia

Clinical Trial Details

NCT number	NCT04164264
Study type	Interventional
Source	University of British Columbia
Contact
Status	Active, not recruiting
Phase	Phase 4
Start date	March 11, 2020
Completion date	December 2024

View Details

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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.