Pharmacokinetics of Micafungin in Patients Intensive Care Unit

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Invasive Fungal Infection

Intervention / Treatment
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* Drug: micafungin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is admitted to an ICU Subject is at least 18 years of age on the day of the first dosing If subject is female: neither pregnant nor able to become pregnant and is not nursing an infant Subject has been treated with micafungin for a maximum of two days before enrolment in this trial Is managed with a central venous catheter or an arterial catheter Exclusion Criteria: Is known to be hypersensitive to echinocandin antifungal agents Documented history of sensitivity to excipients similar to those found in the micafungin preparation Known of positive HIV test or positive hepatitis B or C test in history History of or current abuse of drugs, alcohol or solvents Has previously participated in this trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ICU patient on micafungin<br>ICU patients with an invasive fungal infection on micafungin treatment | Drug: micafungin<br>* 100mg/day infusion in 1 hour<br>* Other names: Mycamine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| micafunigin AUC | AUC0-tau [mg*g/L] of micafungin given to ICU patients. Other pharmacokinetic parameters will be assessed as well. | Day 3 and Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| covariates | 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). | 17 days | 
| exposure | To determine whether adequate exposure is attained in ICU patients | 17 days | 
| number of adverse events | To determine the safety of micafungin in this patient population | 17 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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invasive fungal infection, micafungin, intensive care, pharmacokinetics