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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ICU patient on micafungin | ICU patients with an invasive fungal infection on micafungin treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| micafungin | Drug | 100mg/day infusion in 1 hour |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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All patients receiving micafungin for the treatment or suspicion of an invasive fungal infection will be included. At least 20 patients will be included to obtain 16 evaluable patients. If recruitment of 20 patients is achieved within one year, more patients can be included. A formal sample size cannot be performed for several reasons but the sample size is rather based on the general assumption that 16 patients are sufficient to have a descriptive PK approach.
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| Name | Affiliation | Role |
|---|---|---|
| R Bruggemann | Radboud University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rijstate Hospital | Arnhem | Netherlands | ||||
| Gelderse Vallei Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25963988 | Result | Lempers VJ, Schouten JA, Hunfeld NG, Colbers A, van Leeuwen HJ, Burger DM, Verweij PE, Pickkers P, Bruggemann RJ. Altered Micafungin Pharmacokinetics in Intensive Care Unit Patients. Antimicrob Agents Chemother. 2015 Aug;59(8):4403-9. doi: 10.1128/AAC.00623-15. Epub 2015 May 11. |
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| ID | Term |
|---|---|
| D000072742 | Invasive Fungal Infections |
| ID | Term |
|---|---|
| D009181 | Mycoses |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000077551 | Micafungin |
| ID | Term |
|---|---|
| D055666 | Lipopeptides |
| D008055 | Lipids |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
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blood samples for pharmacokinietic analysis will be collected
| 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 |
| Ede |
| Netherlands |
| Canisius Wilhelmina Ziekenhuis | Nijmegen | Netherlands |
| Radboud University Nijmegen Medical Centre | Nijmegen | Netherlands |
| D054714 |
| Echinocandins |
| D010456 | Peptides, Cyclic |