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

NCT02357407 | Completed Phase 4

• 2 other identifiers: 2014-004193-435RC14_9179
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

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.

Conditions

Infection

Keywords

fluoroquinolones; pharmacokinetic; infections

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Demographic data

  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)

• AUC

  on day-4 of their treatment (steady-state)

• MIC

  on day-4 of their treatment (steady-state)

Study Arms (2)

Patients in intensive care

EXPERIMENTAL

30 patients in intensive care treated with ciprofloxacin IV

Drug: Patients in intensive care : infection treated with ciprofloxacin IV

Osteoarticular infected patients

EXPERIMENTAL

30 patients in orthopedics treated with oral ofloxacin

Drug: Osteoarticular infected patients : infection treated with oral ofloxacin

Interventions

Patients in intensive care : infection treated with ciprofloxacin IV DRUG

8-10 samples per patients on day-4 of their treatment

Also known as: Blood samples

Patients in intensive care

Osteoarticular infected patients : infection treated with oral ofloxacin DRUG

8-10 samples per patients on day-4 of their treatment

Also known as: Blood samples

Osteoarticular infected patients

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (1)

Rennes University Hospital

Rennes, 35033, France

Location

Related 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 infections: The Fluo-pop study. Biomed Pharmacother. 2021 Oct;142:112053. doi: 10.1016/j.biopha.2021.112053. Epub 2021 Aug 19.

  PMID: 34435591 RESULT

MeSH Terms

Conditions

Infections

Interventions

Blood Specimen Collection; Ofloxacin

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Bruno BL Laviolle, MD/PhD

  Rennes University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2015
• First Posted: February 6, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 24, 2023

Record last verified: 2023-05

Locations

FR (1)