Development of an Adjustment Assistance Tool Dosage of Fluoroquinolones in a Population Pharmacokinetic Model

Phase 4

Completed

• Conditions: Infection

• Registration Number: NCT02357407
• Lead Sponsor: Rennes University Hospital

Brief Summary

Fluoroquinolones (FQ) are among pivotal antibiotic treatments in difficult-to-treat infections. Their efficacy has been shown to be linked to the ratio area under the curve (AUC) of their plasma concentrations over the minimum inhibitory concentration (MIC) of the bacteria treated. Eventually, Forrest et al., reported in gram-negative infections that an AUC/MIC above 125 conducted to a 80 to 90% clinical success whereas success decrease to 30 to 40% in patients with an AUC/MIC below this threshold. These results have been reproduced recently by Zelenitsky et al. in intensive care unit (ICU) patients with threshold similar to the one obtained by Forrest et al. Lastly, elevated concentrations of FQ should be related with the onset of adverse events. Thus, therapeutic drug monitoring (TDM) of FQ appears of potential interest, particularly in case of severe infections (intensive care unit (ICU) patients) or complicated and cost-related infections (osteoarticular infected (OAI) patients), with an increasing level of evidence of its use.

However, FQ TDM requires access to the full AUC of the drug with the need of many samples drawn to patients. This appears to be irreconcilable with clinical practice but can be achieved using population pharmacokinetic (PkPop) modelling. PkPop allows estimating pharmacokinetic parameters of the drug by introducing covariates (demographic, biological, clinical...) and modelling inter-individual pharmacokinetic variability. The model created allows then accessing to individual parameters of patients and thus, estimating concentrations and AUC of the FQ. This approach may also be used in clinical practice to determine a limited sampling strategy allowing an adequate estimation of AUC with a minimum of samples.

Detailed Description

Open, prospective, monocentric pharmacokinetic study

Study Timeline

• Study First Submitted: 2015-01-16
• Study First Submitted QC: 2015-02-02
• Study First Posted: 2015-02-06
• Study Start: 2015-06
• Primary Completion: 2016-12
• Study Completion: 2016-12
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-22
• Last Update Posted: 2023-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 31

Inclusion Criteria

• Age over 18 years
• Patients in intensive care : Infection treated with ciprofloxacin IV
• Osteoarticular infected patients : infection treated with oral ofloxacin
• Written consent to participate in the study

Exclusion Criteria

• Pregnancy
• Adults subject to legal protection or deprived of their liberty

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Plasma concentration measurement of ciprofloxacin and ofloxacin	on day-4 of their treatment (steady-state)	measurement between 2 administrations (8-10 samples per patients)

Secondary Outcome Measures

Name	Time	Method
AUC	on day-4 of their treatment (steady-state)
MIC	on day-4 of their treatment (steady-state)
Biological data	on day-4 of their treatment (steady-state)
Clinical data	on day-4 of their treatment (steady-state)
Demographic data	on day-4 of their treatment (steady-state)
Cmax	on day-4 of their treatment (steady-state)

Trial Locations

Locations (1)

Rennes University Hospital; 🇫🇷 Rennes, France