Pharmacokinetics of Micafungin in Patients of Intensive Care Units
Information source: University Hospital, Limoges
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Invasive Candidiasis
Intervention: micafungin (Other)
Phase: Phase 4
Status: Recruiting
Sponsored by: University Hospital, Limoges Overall contact: Pierre MARQUET, MD, Phone: (+33) 5 55 05 61 40, Email: pierre.marquet@unilim.fr
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 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.
Clinical Details
Official title: Pharmacokinetics of Micafungin in Patients of Intensive Care Units
Study design: Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label
Primary outcome: To describe micafungin concentrations over time,
Secondary outcome: To estimate the proportion of patients hospitalized in an ICU achieving the target AUC or AUC/MIC when receiving the recommended regimen
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
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")
Locations and Contacts
Pierre MARQUET, MD, Phone: (+33) 5 55 05 61 40, Email: pierre.marquet@unilim.fr
CHU de Montpellier, Montpellier 34295, France; Recruiting Boris Jung
Additional Information
Starting date: June 2014
Last updated: June 17, 2014
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