Candida Infections Clinical Trial
Official title:
Impact of a Loading Dose of Caspofungin on Pharmacokinetic and Pharmacodynamic Parameters Target Achievements for Severe Candida Infections in ICU Patients
Echinocandins are the drug of choice in severe candida infections. Efficacy of echinocandins
is related to concentration and area under the curve (AUC) of the drug.
Available pharmacokinetic studies found that concentration of echinocandins mainly
caspofungin is sub-optimal in severe candida infections in intensive care unit (ICU)
patients.
Higher dose of caspofungin has been proven to be safe in critically ill patients but its
impact on the ability to reach PK/PD target is unknown.
The aim of this study is to evaluate the impact of a loading dose of caspofungin on PK/PD
parameters within the first 24-hours.
Invasive fungal infections are associated to a high mortality rate in ICU, partly because of
a delayed treatment.
PK/PD targets for caspofungin are the peak concentration over minimal inhibitory
concentration (MIC) ratio which should reach 10 and the area under the inhibitory curve
(AUIC) which should be over 200. High distribution volume in ICU patients and increase of
MICs due to extensive use of antifungal agents make optimal concentration difficult to
obtain. High doses up to 150mg of caspofungin have been reported to be safe. Thus, in our
unit, a loading dose of 140mg of caspofungin is a standard practice but was never rigorously
evaluated.
The aim of the present study is to measure the impact of a loading dose of 140mg of
caspofungin on the pharmacokinetic parameters in the first 24 hours of treatment.
The AUIC and maximal concentration (CMax) / (MIC) according to the recovered yeasts will be
measured. The investigators also planned a Monte-Carlo simulation using MICs obtained from
clinically relevant candida strains isolated in Bichat and Grenoble hospitals in order to
evaluate the percentage of patients appropriately treated within the first 24 hours
according to Candida species and previous use of antifungals.
Recovered strains from epidemiological studies will be used for PKPD modelling and will use
s. A second Monte-Carlo simulation will be done using data from the Amarcand 2 study.
All MICs will be determined using E-test ( Biomerieux® KIT's) without specifying any
breakpoints as MICs and not breakpoints per se will be used.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02631954 -
Phase I Clinical Trial for Comparison of Pharmacokinetic Characteristics of Vorico Injection 200mg(Voriconazole) and Vfend® IV 200mg for Single Dose Crossover Intravenous Infusion in Healthy Volunteers
|
Phase 1 |