Clinical trial NCT01783379: Pharmacokinetics of Micafungin in Patients Intensive Care Unit
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Invasive Fungal Infection
Keywords: invasive fungal infection
micafungin
intensive care
pharmacokinetics
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2013-02-04
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patient is admitted to an ICU
2. Subject is at least 18 years of age on the day of the first dosing
3. If subject is female: neither pregnant nor able to become pregnant and is not nursing an infant
4. Subject has been treated with micafungin for a maximum of two days before enrolment in this trial
5. Is managed with a central venous catheter or an arterial catheter

Exclusion Criteria:

1. Is known to be hypersensitive to echinocandin antifungal agents
2. Documented history of sensitivity to excipients similar to those found in the micafungin preparation
3. Known of positive HIV test or positive hepatitis B or C test in history
4. History of or current abuse of drugs, alcohol or solvents
5. Has previously participated in this trial

Primary outcomes:
measure: micafunigin AUC
timeFrame: Day 3 and Day 7
Secondary outcomes:
measure: covariates
timeFrame: 17 days
measure: exposure
timeFrame: 17 days
measure: number of adverse events
timeFrame: 17 days
Other outcomes:
Locations:
city: Arnhem
country: Netherlands
facility: Rijstate Hospital
city: Ede
country: Netherlands
facility: Gelderse Vallei Hospital
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Centre
Study officials:
affiliation: Radboud University Medical Center
name: R Bruggemann
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.