Clinical trial NCT03134521: Population Pharmacokinetic Analysis of Daptomycin in Patients With Osteoarticular Infections
Official title: Population Pharmacokinetic Analysis of Daptomycin in Patients With Osteoarticular Infections
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Bone Infection
Joint Infection
Keywords: bone and joint infection
daptomycin
population pharmacokinetics
Glycoprotein-P (PgP)
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2017-05-01
Enrollment: 189
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients having bone or joint infection, with or without implant, having an antibiotherapy with daptomycin

Brief summary: Daptomycin is validated as a treatment of bone and joint infections by the Infectious Disease Society of America. However, most of studies did not investigate daptomycin pharmacokinetics in this indication while it is known that efficacy and toxicity concentration studies show a close therapeutic margin.

Evaluation of P-Glycoprotein (P-gp), a transmembrane transport protein, has demonstrated its influence on the concentration and intracellular activity of daptomycin. Recent work has linked the genetic polymorphism of P-gp to the pharmacokinetics of daptomycin, which may explain inter-individual variability but requires further explorations. Previous studies demonstrated existence of interindividual variabilities as sex, renal function and p-glycoprotein polymorphism couple with an intraindividual variabilities unexplained yet.

A population approach will be used to determinate the pharmacokinetics factors, their intra and interindividual variabilities, the parameters associated to those variabilities (as the p glycoprotein).

The investigator's goal is to evaluate different posology and to try to increase daptomycin efficacy and security in bone and joint infection.


Eligibility criteria: Inclusion Criteria:

Patients

* having had a bone or joint infection, with or without implant,
* having an antibiotherapy with daptomycin between December 2012 and December 2016 at the Croix-Rousse hospital
* are at least 18 years old

Exclusion Criteria:

* None

Primary outcomes:
measure: Peak plasma concentration (Cmax)
timeFrame: Month 6
Secondary outcomes:
measure: Area under the concentration-time curve
timeFrame: up to 6 months
measure: typical daptomycin clearance and volume of distribution in the population
timeFrame: Month 6
measure: Mean daptomycine plasma clearance
timeFrame: Month 6
measure: Mean daptomycine volume of distribution
timeFrame: Month 6
measure: Inter-individual coefficient of variation of daptomycin clearance
timeFrame: Month 6
measure: Inter-individual coefficient of variation of daptomycin volume of distribution
timeFrame: Month 6
measure: Intra-individual coefficient of variation of daptomycin clearance
timeFrame: Month 6
measure: Intra-individual coefficient of variation of daptomycin volume of distribution
timeFrame: Month 6
measure: influence of demographic and biological covariates on pharmacokinetics (e.g. : renal function, gender)
timeFrame: Month 6
measure: influence of p-glycoprotein pharmacogenetics on daptomycin pharmacokinetics
timeFrame: Month 6
Other outcomes:
Locations:
Study officials:
affiliation: Hospices Civils de Lyon - Hopital de la Croix Rousse
name: Tristan Ferry
role: PRINCIPAL_INVESTIGATOR
References: