Establish the pharmacokinetic parameters of micafungin in critically ill patients and determine whether pharmacokinetic parameters and plasma concentrations of micafungin correlate with disease severity.
ID
Source
Brief title
Condition
- Fungal infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the correlation of the pharmacokinetic parameters
and plasma concentration of micafungin with disease severity scores.
Secondary outcome
1) Pharmacokinetic parameters of micafungin in ICU patients.
2) Time (in days) to culture conversion.
3) Correlation of the plasma concentration of micafungin with response to
treatment.
4) Correlation of the plasma concentration of micafungin with inflammation
parameters.
5) AUC/MIC ratio and Cmax/MIC ratio.
6) Constructing a pharmacokinetic model of micafungin in critically ill
patients.
Background summary
In adult patients, the overall mortality rate attributable to candidemia varies
from 14.5 to 49%. Furthermore, candidemia is associated with an increase in
length of hospital stay and hospital charges. Intensive care unit (ICU)
patients are especially at risk for invasive candidiasis due to the presence of
risk factors. A study of micafungin in ICU versus non-ICU patients showed a
significantly lower treatment success in ICU patients (62.5% success) compared
with non-ICU patients (85% success). The Acute Physiology and Chronic Health
Evaluation II score for disease severity was a potential explanatory factor
associated with treatment success. Furthermore, it is known that in critically
ill patients, alterations in function of various organs and body systems
influences the pharmacokinetics and hence the plasma concentration of a drug.
The pharmacokinetic parameters of micafungin in critically ill patients are
most likely different, but this had not been specifically studied.
Study objective
Establish the pharmacokinetic parameters of micafungin in critically ill
patients and determine whether pharmacokinetic parameters and plasma
concentrations of micafungin correlate with disease severity.
Study design
Observational pharmacokinetic study. On day 4 (± 1 day) of treatment with
micafungin, a full pharmacokinetic profile of micafungin will be obtained.
Blood samples are taken just before administration of micafungin and 1, 2, 3,
4, 6, 8, 12 and 24 hours after the start of the infusion. Besides, trough
levels will be followed every three days during treatment on the ICU, with a
maximum of 28 days, to evaluate potential fluctuations in micafungin
concentration over time. On the day the full micafungin curve is obtained,
blood samples are drawn for determination of procalcitonin, interleukin-6 and
interleukin-8 to assess correlation of micafungin plasma concentration with
inflammation parameters. Different disease severity scores (APACHE II, APACHE
IV, LODS, MODS, MPM II, ODIN, SAPS 3, SOFA) will be calculated on the day the
full pharmacokinetic profile of micafungin is obtained. The calculation of the
different scores is based on clinical parameters that are routinely recorded
for ICU patients.
Study burden and risks
Results of this study can contribute to practical decision rules for
therapeutic drug monitoring and future dosing schedules in critically ill
patients treated with micafungin. The extra blood samples needed to study the
pharmacokinetic parameters are no extra burden as these patients already have
an indwelling vascular catheter.
This study cannot be conducted without these patients as they are the subject
of investigation.
Hanzeplein 1
Groningen 9700 RB
NL
Hanzeplein 1
Groningen 9700 RB
NL
Listed location countries
Age
Inclusion criteria
Treatment with micafungin
Admission to an ICU
Age >= 18 years
Invasive candidiasis
Exclusion criteria
Blood sampling not possible.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | clinicaltrials.gov |
| CCMO | NL39246.042.12 |