Pharmacokinetics of Micafungin in Patients of Intensive Care Units (MI-K)

University of Limoges (UL)

Status and phase

Completed

Phase 4

Conditions

Invasive Candidiasis

Treatments

Other: micafungin

Study type

Interventional

Funder types

Other

Identifiers

NCT02164890

I13025

Details and patient eligibility

About

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 healthy volunteers, it was observed that CL/F of MCF presents a high interpatient variability.(2)
Whether most ICUs patients achieve optimal AUC/MIC ratio thresholds at standard doses has not been investigated so far. In particular, lower AUCs might be reached in patients having the highest VC/F values. Such patients would then be at risk of therapy failure and would benefit from individualized-dosing strategies.

In this context, the study of the pharmacokinetics of MCF in critically ill patients seems to be necessary.

Enrollment

60 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Critically ill patients hospitalized in an ICU, with suspected or proven invasive fungal infections, for whom the decision has been made to start a treatment based on MCF.
Age > 18 years.
Patients willing to give their written informed consent for their participation to the study.
Patients affiliated to the French social security system or equivalent.

Exclusion criteria

Patient for whom a treatment based on MCF has already been started
Patient who have benefited from bone marrow transplantation
Age < 18 years
Patient under legal protection
Patient deprived of liberty
Pregnant or breast-feeding woman or woman of childbearing potential without efficient contraception (based on declaration)
Patient with any altered mental status or any psychiatric condition that would interfere with the understanding of the study
Patient enrolled in another clinical trial testing drugs or therapeutic strategies (including the so-called "exclusion period")