Pharmacokinetics of Micafungin in Patients Intensive Care Unit (MIMIC)
In this trial, our goal is to determine the pharmacokinetics of micafungin in a non-selected cohort of patients with suspected or proven invasive fungal infections. Patients will receive micafungin for the period necessary to achieve clinical and / or mycological cure. An attempt will be made to have 2 PK curves, one full and one limited sampling on days 3 (n=9) and 7 (n=5). Furthermore, we will be able to determine intra-individual variability. On non-PK days, trough samples will be taken to determine the time to steady state. All samples will be taken just prior to the morning dose of micafungin. All infusion rates will be according to the SPC label information. Patients are considered to be evaluable if at least the first PK curve has been completed. Two moments of PK analysis will enable us to determine whether there is an increase over time in exposure if steady state has not been reached.
|Study Design:||Observational Model: Case-Only
Time Perspective: Prospective
|Official Title:||Pharmacokinetics of Micafungin (Mycamine ®) Given Intravenously as Therapy to Patients With an Invasive Fungal Infection in the Intensive Care Unit - a Search for Co-variates|
- micafunigin AUC [ Time Frame: Day 3 and Day 7 ] [ Designated as safety issue: No ]AUC0-tau [mg*g/L] of micafungin given to ICU patients. Other pharmacokinetic parameters will be assessed as well.
- covariates [ Time Frame: 17 days ] [ Designated as safety issue: No ]co-variates of influence on the pharmacokinetics of micafungin. Specific co-variates are of high interest to the researchers: high body weight (including obese patients, defined as BMI> 30 kg/m2), hypo-albuminaemia, clearance pathways, impact of extracorporeal clearance system (ECMO, CVVH).
- exposure [ Time Frame: 17 days ] [ Designated as safety issue: No ]To determine whether adequate exposure is attained in ICU patients
- number of adverse events [ Time Frame: 17 days ] [ Designated as safety issue: Yes ]To determine the safety of micafungin in this patient population
Biospecimen Retention: Samples Without DNA
blood samples for pharmacokinietic analysis will be collected
|Study Start Date:||January 2013|
|Study Completion Date:||March 2014|
|Primary Completion Date:||March 2014 (Final data collection date for primary outcome measure)|
ICU patient on micafungin
ICU patients with an invasive fungal infection on micafungin treatment
100mg/day infusion in 1 hour
Other Name: Mycamine
Whilst micafungin (Mycamine®) has much to offer, little is known about its pharmacokinetic profile in ICU patients with specific co-morbidities such as obesity, hypoalbumenia, and severe liverfunction disturbances. Also, ICU patients are known to experience changes in pharmacokinetics (PK) due to changes in hemodynamics, extracorporeal elimination techniques, interacting comedication, etc. Based on criteria outlined below, micafungin may prove to be the drug of choice in this cohort of patients. Therefore it seems prudent to conduct a trial in a cohort of patients who receive micafungin but with co-variates that may be of influence to the pharmacokinetic profile. To build a valid pharmacokinetic model, all patients on micafungin will be included in the analysis and used for model building. Co-variates that will be explored are at least: obesitas, liverfunction, albumin, creatinin-clearance. Simulations will be performed to determine if adequate exposure is reached under different patho-physiological conditions.
In conclusion: this trial is on determining the PK of micafungin in a non-selected cohort of patients with suspected or proven invasive fungal infections. Most important covariates will be modelled using advanced mathematical techniques. Micafungin may prove to be beneficial over the other two echinocandins in terms of limited factors that impact PK. This has to be proven in a prospective trial.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01783379
|Gelderse Vallei Hospital|
|Radboud University Nijmegen Medical Centre|
|Canisius Wilhelmina Ziekenhuis|
|Principal Investigator:||R Bruggemann||Radboud University|