Pharmacokinetics of Micafungin in Patients Intensive Care Unit (MIMIC)

This study is currently recruiting participants.
Verified October 2013 by Radboud University
Sponsor:
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01783379
First received: January 9, 2013
Last updated: October 22, 2013
Last verified: October 2013
  Purpose

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 Intervention
Invasive Fungal Infection
Drug: micafungin

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • micafunigin AUC [ Time Frame: Day 3 and Day 7 ] [ Designated as safety issue: No ]
    AUC0-tau [mg*g/L] of micafungin given to ICU patients. Other pharmacokinetic parameters will be assessed as well.


Secondary Outcome Measures:
  • covariates [ Time Frame: 17 days ] [ Designated as safety issue: No ]
    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).

  • exposure [ Time Frame: 17 days ] [ Designated as safety issue: No ]
    To determine whether adequate exposure is attained in ICU patients

  • number of adverse events [ Time Frame: 17 days ] [ Designated as safety issue: Yes ]
    To determine the safety of micafungin in this patient population


Biospecimen Retention:   Samples Without DNA

blood samples for pharmacokinietic analysis will be collected


Estimated Enrollment: 20
Study Start Date: January 2013
Estimated Study Completion Date: February 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01783379

Contacts
Contact: R Bruggemann +31243616405 r.bruggemann@akf.umcn.nl
Contact: V Lempers +31243616405 v.lempers@akf.umcn.nl

Locations
Netherlands
Rijstate Hospital Not yet recruiting
Arnhem, Netherlands
Contact: H. van Leeuwen, dr.         
Principal Investigator: H. van Leeuwen, dr.         
Gelderse Vallei Hospital Not yet recruiting
Ede, Netherlands
Contact: A. van Zanten, dr.         
Principal Investigator: A. van Zanten, dr.         
Radboud University Nijmegen Medical Centre Recruiting
Nijmegen, Netherlands
Contact: R Bruggemann    +31243616405    r.bruggemann@akf.umcn.nl   
Sub-Investigator: R Pickkers         
Canisius Wilhelmina Ziekenhuis Recruiting
Nijmegen, Netherlands
Contact: J Schouten    +31243657657    j.schouten@cwz.nl   
Principal Investigator: J Schouten         
Erasmus University Medical Centre Not yet recruiting
Rotterdam, Netherlands
Sponsors and Collaborators
Radboud University
Investigators
Principal Investigator: R Bruggemann Radboud University
  More Information

No publications provided

Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01783379     History of Changes
Other Study ID Numbers: UMCN AKF 12.05
Study First Received: January 9, 2013
Last Updated: October 22, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
invasive fungal infection
micafungin
intensive care
pharmacokinetics

Additional relevant MeSH terms:
Mycoses
Micafungin
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 15, 2014