Pharmacokinetics of Micafungin in Patients Intensive Care Unit (MIMIC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01783379
Recruitment Status : Completed
First Posted : February 4, 2013
Last Update Posted : April 30, 2014
Information provided by (Responsible Party):
Radboud University

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.

Condition or disease Intervention/treatment
Invasive Fungal Infection 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
Actual Enrollment : 20 participants
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
Study Start Date : January 2013
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

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 Name: Mycamine

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

Secondary Outcome Measures :
  1. covariates [ Time Frame: 17 days ]
    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).

  2. exposure [ Time Frame: 17 days ]
    To determine whether adequate exposure is attained in ICU patients

  3. number of adverse events [ Time Frame: 17 days ]
    To determine the safety of micafungin in this patient population

Biospecimen Retention:   Samples Without DNA
blood samples for pharmacokinietic analysis will be collected

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01783379

Rijstate Hospital
Arnhem, Netherlands
Gelderse Vallei Hospital
Ede, Netherlands
Canisius Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands
Sponsors and Collaborators
Radboud University
Principal Investigator: R Bruggemann Radboud University

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Radboud University Identifier: NCT01783379     History of Changes
Other Study ID Numbers: UMCN AKF 12.05
First Posted: February 4, 2013    Key Record Dates
Last Update Posted: April 30, 2014
Last Verified: April 2014

Keywords provided by Radboud University:
invasive fungal infection
intensive care

Additional relevant MeSH terms:
Invasive Fungal Infections
Antifungal Agents
Anti-Infective Agents