Population Pharmacokinetic Model of Rifampicin in Staphylococcal Osteoarticular Infections
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorGroupe Hospitalier Diaconesses Croix Saint-Simon
About this trial
Staphylococcal osteoarticular infections (OAIs), including prosthetic joint infections and chronic osteomyelitis, represent a major cause of morbidity. Rifampicin is a key bactericidal antibiotic effective against staphylococcal biofilm. However, its pharmacokinetics exhibit substantial inter-individual variability due to complex hepatic metabolism and drug interactions. Currently, no prospective population pharmacokinetic (PopPK) model of rifampicin combined with levofloxacin or ciprofloxacin exists in patients with OAIs. Objectives:
The primary objective of this study is to develop a population pharmacokinetic model of oral rifampicin in patients undergoing medico-surgical treatment for staphylococcal osteoarticular infections. Secondary objectives include evaluating the pharmacokinetics of the partner antibiotic (levofloxacin or ciprofloxacin), investigating the correlation between antibiotic exposure metrics (AUC, Cmax, AUC/MIC) and clinical/biological tolerance, and assessing 1-year infection relapse-free survival and resistance emergence. Study Design:
Prospective, single-center, interventional study with minimal risks and constraints (RIPH 2) involving 40 participants recruited at the Reference Center for Complex Osteoarticular Infections (CRIOAC).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patient informed about the study and signed written consent obtained
Male or female participant aged 18 years or older
Staphylococcal osteoarticular infection (prosthetic joint infection of hip, knee, or shoulder; chronic osteomyelitis; or native joint infection) susceptible to rifampicin and levofloxacin or ciprofloxacin
Indication for combined medico-surgical treatment of the osteoarticular infection
Disqualifiers
Septic shock requiring vasopressor support
Prior rifampicin treatment within 1 month preceding inclusion
Contraindication to rifampicin (known allergy, major drug interaction, or hepatic cirrhosis)
End-stage renal disease on chronic dialysis
Trial design
Design model
Single group
Treatments tested in this trial
This study focuses on the pharmacokinetics of rifampicin and levofloxacin or ciprofloxacin, which are used in the treatment of osteoarticular infections caused by susceptible staphylococci as part of
DrugThis study primarily aims to evaluate the pharmacokinetics of rifampicin, but also of one of the two partner antibiotics, levofloxacin or ciprofloxacin, used in the treatment of staphylococcal osteoarticular infections, whether or not they are present in the body. To this end, 12 blood samples, totaling 60 ml per patient, will be required. These samples will be collected specifically for this clinical research. The remainder of the study will be conducted as part of standard patient care.
Treatment groups
40 Participants
are divided into 1 treatment groupGroup A: All patients treated at the GHDCSS Reference Center for Complex Osteoarticular Infections for jointExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Area Under the Plasma Concentration-Time Curve (AUC) of Rifampicin
Area under the plasma concentration-time curve of oral rifampicin, estimated using a population pharmacokinetic non-linear mixed-effects model (NONMEM).
Time frame
Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy2
Peak Plasma Concentration (Cmax) of Rifampicin
Maximum observed plasma concentration (Cmax) of oral rifampicin, measured following administration.
Time frame
Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy3
Apparent Oral Clearance (CL/F) of Rifampicin
Apparent oral clearance (CL/F) of rifampicin estimated using a population pharmacokinetic model (NONMEM), including evaluation of inter-individual variability and covariate effects.
Time frame
Through 4 weeks post-initiation of antibiotic therapy4
Apparent Volume of Distribution (V/F) of Rifampicin
Apparent volume of distribution (V/F) of rifampicin estimated using a population pharmacokinetic model (NONMEM), including evaluation of inter-individual variability and covariate effects.
Time frame
Through 4 weeks post-initiation of antibiotic therapySecondary outcomes
1
Incidence of Clinical and Biological Adverse Events Related to Rifampicin Exposure
Proportion of patients experiencing clinical or biological adverse events (recorded in CRF) evaluated in relation to rifampicin Cmax and AUC.
Time frame
Through 4 weeks post-initiation of antibiotic therapy2
Infection Relapse-Free Survival at 1 Year Relative to Rifampicin AUC/MIC Ratio
Time to staphylococcal infection relapse over a 1-year follow-up period, analyzed in relation to the rifampicin AUC/MIC (Minimum Inhibitory Concentration) ratio.
Time frame
12 months post-initiation of antibiotic therapy3
Emergence of Rifampicin Resistance at Relapse
Assessment of rifampicin MIC (determined by E-test) at the time of infection relapse compared to baseline, evaluated according to Cmax/MIC and AUC/MIC ratios.
Time frame
12 months post-initiation of antibiotic therapy4
Peak Plasma Concentration (Cmax) of Partner Antibiotic
Maximum observed plasma concentration (Cmax) of the partner antibiotic (levofloxacin or ciprofloxacin) administered in combination with rifampicin.
Time frame
Day 8/10 and Day 28/32 post-initiation of antibiotic therapySponsors and contacts
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Source ClinicalTrials.gov