Population Pharmacokinetic Model of Rifampicin in Staphylococcal Osteoarticular Infections

NCT07788404 | Recruiting

• 2 other identifiers: RIPH2-Ciné-RIF_CRIOA_1_20232023-A00530-45
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Prosthetic Joint Infection; Osteomyelitis; Staphylococcal Infections

Keywords

Rifampicin; Levofloxacin; Ciprofloxacin; Population Pharmacokinetic; Biofilm

Outcome Measures

Primary Outcomes (4)

• 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).

  Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy

• Peak Plasma Concentration (Cmax) of Rifampicin

  Maximum observed plasma concentration (Cmax) of oral rifampicin, measured following administration.

  Day 2/3, Day 8/10, and Day 28/32 post-initiation of antibiotic therapy

• 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.

  Through 4 weeks post-initiation of antibiotic therapy

• 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.

  Through 4 weeks post-initiation of antibiotic therapy

Secondary Outcomes (7)

• Incidence of Clinical and Biological Adverse Events Related to Rifampicin Exposure

  Through 4 weeks post-initiation of antibiotic therapy

• Infection Relapse-Free Survival at 1 Year Relative to Rifampicin AUC/MIC Ratio

  12 months post-initiation of antibiotic therapy

• Emergence of Rifampicin Resistance at Relapse

  12 months post-initiation of antibiotic therapy

• Peak Plasma Concentration (Cmax) of Partner Antibiotic

  Day 8/10 and Day 28/32 post-initiation of antibiotic therapy

• Trough Plasma Concentration (Cmin) of Partner Antibiotic

  Day 8/10 and Day 28/32 post-initiation of antibiotic therapy

Study Arms (1)

All patients treated at the GHDCSS Reference Center for Complex Osteoarticular Infections for joint

EXPERIMENTAL

Drug: 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

Interventions

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 DRUG

This 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.

All patients treated at the GHDCSS Reference Center for Complex Osteoarticular Infections for joint

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Septic shock requiring vasopressor support
• Contraindication to rifampicin (known allergy, major drug interaction, or hepatic cirrhosis)
• End-stage renal disease on chronic dialysis
• Pregnant or breastfeeding woman
• Adult patient unable or unfit to give informed consent
• Subject deprived of liberty by judicial or administrative decision
• Subject not affiliated with or beneficiary of a national social security scheme

Sponsors & Collaborators

• Groupe Hospitalier Diaconesses Croix Saint-Simon: lead

Study Sites (1)

Groupe hospitalier Diaconesses Croix Saint Simon

Paris, Paris, 75020, France

RECRUITING

MeSH Terms

Conditions

Osteomyelitis; Staphylococcal Infections

Interventions

Levofloxacin; Ciprofloxacin

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2026
• First Posted: August 26, 2026
• Study Start: June 10, 2023
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: August 26, 2026

Record last verified: 2026-08

Locations

FR (1)