Pharmacokinetics of Micafungin in Patients Intensive Care Unit (MIMIC)

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

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 Overview

• Status: Completed
• Conditions: Invasive Fungal Infection
• Intervention / Treatment: Drug: micafungin

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.

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Netherlands
  • Arnhem, Netherlands
    • Rijstate Hospital
  • Ede, Netherlands
    • Gelderse Vallei Hospital
  • Nijmegen, Netherlands
    • Canisius Wilhelmina Ziekenhuis
  • Nijmegen, Netherlands
    • Radboud University Nijmegen Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
ICU patient on micafungin; ICU patients with an invasive fungal infection on micafungin treatment	Drug: micafungin; 100mg/day infusion in 1 hour; Other Names: Mycamine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: R Bruggemann, Radboud University Medical Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: January 9, 2013
• First Submitted That Met QC Criteria: January 31, 2013
• First Posted (Estimate): February 4, 2013

Study Record Updates

• Last Update Posted (Actual): November 30, 2020
• Last Update Submitted That Met QC Criteria: November 26, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: pharmacokinetics; intensive care; invasive fungal infection; micafungin
• Additional Relevant MeSH Terms: Bacterial Infections and Mycoses; Infections; Mycoses; Invasive Fungal Infections; Anti-Infective Agents; Antifungal Agents; Micafungin
• Other Study ID Numbers: UMCN AKF 12.05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No