Pharmacokinetics of Micafungin in Patients of Intensive Care Units

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.

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Key information

Conditions

Invasive Candidiasis Bacterial Infections and Mycoses Candidiasis Candidiasis, Invasive Infections Invasive Fungal Infections Mycoses

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

CHU de Montpellier

Montpellier, 34295, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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")

Treatment and study plan

micafungin

Other

This is a pharmacokinetic study where a total number of 14 blood samples will be drawn per patient. Clinical and biological data will be concomitantly collected.

Primary outcomes

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.

Secondary outcomes

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)

Sponsors and collaborators

Lead sponsor

University Hospital, Limoges

Other

Registry information

Acronym: MI-K

Important dates

Study start: 2014
Primary completion: 2015
Study completion: 2016
First posted: Jun 17, 2014
Registry last updated: Nov 21, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

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