Clinical Trial: Pharmacokinetics of Micafungin in Patients of Intensive Care Units

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Pharmacokinetics of Micafungin in Patients of Intensive Care Units

Brief Summary:

Invasive fungal infections (IFIs) are a frequent cause of morbidity and mortality in high-risk patients, such as immunocompromised patients. Candida is currently the predominant fungal pathogen in these patient populations and is associated with significant morbidity and a high mortality.

Micafungin (MCF) is a semisynthetic compound belonging to the new class of antifungal agents, the echinocandin lipopeptides, that has potent in vitro and experimental in vivo activity against a variety of pathogenic Candida species and Aspergillus species. Its applied indications are so the treatment and/or the prophylaxis of Candida and Aspergillus infections. MCF is currently licensed for the treatment of candidiasis at doses of either 100 or 150 mg a day.

The efficacy of MCF is linked to the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC0-24/ MIC ratio).

On one hand:

- It was demonstrated that 98% of invasive candidiasis patients with a MCF AUC/MIC ratio between 3 and 12 achieve microbiological clearance, as opposed to only 85% of those with an AUC/MIC ratio < 3. In the case of infections by Candida parapsilosis, which exhibits drug MICs that are 50- to100-fold higher, 100% of patients with an AUC/MIC ratio >285 achieve microbiological clearance, as opposed to 82% of those below that exposure level.(1)

On the other hand:

• It is well known that patients of intensive care units (ICU) are characterized by particular pharmacokinetic parameters with higher apparent volume of distribution (VC/F) and/or higher apparent systemic clearance (CL/F). In a population of
  

  Detailed Summary:
  Sponsor: University Hospital, Limoges
  

  Current Primary Outcome: To describe micafungin concentrations over time, [ Time Frame: 3 weeks ]

  The evaluation of the PK model performance will be based on its ability:

  • To describe micafungin concentrations over time,
  • To explain the sources of inter-individual PK variability. It will be done by the calculation of the bias between concentrations predicted using the model and observed concentrations.
  
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome: To estimate the proportion of patients hospitalized in an ICU achieving the target AUC or AUC/MIC when receiving the recommended regimen [ Time Frame: 3 weeks ]

  The estimation of the proportion of patients hospitalized in an ICU achieving the target AUC or AUC/MIC when receiving the recommended regimen will be based on the determination of exposure indices (AUC) and mycological characteristics (fungus and its MIC)
  
  
  

  Original Secondary Outcome: Same as current
  
  Information By: University Hospital, Limoges
  

  Dates:
  Date Received: June 13, 2014
  Date Started: June 2014
  Date Completion: December 2016
  Last Updated: August 19, 2016
  Last Verified: June 2016