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

Infection Clinical Trial

— FLUO-POP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02357407
• Other study ID #: 2014-004193-4
• Secondary ID: 35RC14_9179
• Status: Completed
• Phase: Phase 4
• Start date: June 2015
• Est. completion date: December 2016

Study information

• Verified date: May 2023
• Source: Rennes University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Open, prospective, monocentric pharmacokinetic study

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Infection
• Infections

Intervention

Drug:
• Patients in intensive care : infection treated with ciprofloxacin IV
8-10 samples per patients on day-4 of their treatment
• Osteoarticular infected patients : infection treated with oral ofloxacin
8-10 samples per patients on day-4 of their treatment

Locations

Country	Name	City	State
France	Rennes University Hospital	Rennes

Sponsors (1)

Lead Sponsor	Collaborator
Rennes University Hospital

Country where clinical trial is conducted

France, 

References & Publications (1)

Lemaitre F, Fily F, Foulquier JB, Revest M, Jullien V, Petitcollin A, Tattevin P, Tron C, Polard JL, Verdier MC, Comets E, Huten D, Arvieux C, Bellissant E, Laviolle B. Development of a dosing-adjustment tool for fluoroquinolones in osteoarticular infecti — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma concentration measurement of ciprofloxacin and ofloxacin	measurement between 2 administrations (8-10 samples per patients)	on day-4 of their treatment (steady-state)
Secondary	Demographic data		on day-4 of their treatment (steady-state)
Secondary	Biological data		on day-4 of their treatment (steady-state)
Secondary	Clinical data		on day-4 of their treatment (steady-state)
Secondary	AUC		on day-4 of their treatment (steady-state)
Secondary	MIC		on day-4 of their treatment (steady-state)
Secondary	Cmax		on day-4 of their treatment (steady-state)