## Protocol Section
### Identification Module
**NCT ID:** NCT01783379

**Acronym:** MIMIC

**Brief Title:** 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

#### Organization Study ID Info
**ID:** UMCN AKF 12.05
#### Organization
**Class:** OTHER
**Full Name:** Radboud University Medical Center
### Status Module
#### Completion Date
**Date:** 2014-03

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2020-11-30

**Type:** ACTUAL

**Last Update Submit Date:** 2020-11-26

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2014-03

**Type:** ACTUAL

#### Start Date
**Date:** 2013-01

**Status Verified Date:** 2020-11

#### Study First Post Date
**Date:** 2013-02-04
**Type:** ESTIMATED
**Study First Submit Date:** 2013-01-09
**Study First Submit QC Date:** 2013-01-31
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Radboud University Medical Center

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Invasive Fungal Infection

**Keywords:**

- invasive fungal infection

- micafungin

- intensive care

- pharmacokinetics

### Design Module

#### Bio Spec

**Description:** blood samples for pharmacokinietic analysis will be collected

**Retention:** SAMPLES_WITHOUT_DNA

#### Design Info

**Observational Model:** CASE_ONLY

**Time Perspective:** PROSPECTIVE

#### Enrollment Info

**Count:** 20

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** ICU patients with an invasive fungal infection on micafungin treatment

**Intervention Names:**

- Drug: micafungin

**Label:** ICU patient on micafungin

### Interventions

#### Intervention 1

**Arm Group Labels:**

- ICU patient on micafungin

**Description:** 100mg/day infusion in 1 hour

**Name:** micafungin

**Other Names:**

- Mycamine

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** AUC0-tau \[mg\*g/L\] of micafungin given to ICU patients. Other pharmacokinetic parameters will be assessed as well.

**Measure:** micafunigin AUC

**Time Frame:** Day 3 and Day 7

#### Secondary Outcomes

**Description:** 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).

**Measure:** covariates

**Time Frame:** 17 days

**Description:** To determine whether adequate exposure is attained in ICU patients

**Measure:** exposure

**Time Frame:** 17 days

**Description:** To determine the safety of micafungin in this patient population

**Measure:** number of adverse events

**Time Frame:** 17 days

### Eligibility Module

**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

**Minimum Age:** 18 Years

**Sampling Method:** NON_PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

**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.

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Arnhem

**Country:** Netherlands

**Facility:** Rijstate Hospital

**Location 2:**

**City:** Ede

**Country:** Netherlands

**Facility:** Gelderse Vallei Hospital

**Location 3:**

**City:** Nijmegen

**Country:** Netherlands

**Facility:** Canisius Wilhelmina Ziekenhuis

**Location 4:**

**City:** Nijmegen

**Country:** Netherlands

**Facility:** Radboud University Nijmegen Medical Centre

#### Overall Officials

**Official 1:**

**Affiliation:** Radboud University Medical Center

**Name:** R Bruggemann

**Role:** PRINCIPAL_INVESTIGATOR

### References Module

#### 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.

**PMID:** 25963988

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000001423

- Term: Bacterial Infections and Mycoses

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

### Condition Browse Module - Browse Leaves

- ID: M10283

- Name: Infections

- Relevance: HIGH

- As Found: Infection

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: HIGH

- As Found: Fungal Infections

- ID: M1099

- Name: Invasive Fungal Infections

- Relevance: HIGH

- As Found: Invasive Fungal Infections

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007239

- Term: Infections

- ID: D000009181

- Term: Mycoses

- ID: D000072742

- Term: Invasive Fungal Infections

### Intervention Browse Module - Ancestors

- ID: D000000935

- Term: Antifungal Agents

- ID: D000000890

- Term: Anti-Infective Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1829

- Name: Micafungin

- Relevance: HIGH

- As Found: AMP

- ID: M6252

- Name: Clotrimazole

- Relevance: LOW

- As Found: Unknown

- ID: M11796

- Name: Miconazole

- Relevance: LOW

- As Found: Unknown

- ID: M4254

- Name: Antifungal Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077551

- Term: Micafungin

### Misc Info Module

- Version Holder: 2024-05-24
