Pharmacokinetics of Fluconazole IV as Prophylaxis or Therapy to ICU Patients

Candidiasis Clinical Trial

— PACIFIC  

Official title:

Pharmacokinetics of Fluconazole Given Intravenously as Prophylaxis or Therapy to Patients With an Invasive Fungal Infection in the Intensive Care Unit (PACIFIC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02666716
• Other study ID #: UMCN-AKF14.06
• Status: Completed
• Start date: May 2015
• Est. completion date: March 2016

Study information

• Verified date: December 2020
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The pharmacokinetics of fluconazole are expected to be different in ICU patients compared to non-ICU patients. The investigators will determine fluconazole and free fluconazole concentrations in 20 ICU patients, who will get intravenous fluconazole as standard care. Switching to oral/enteral fluconazol is allowed after day 3.

A full pharmacokinetic curve will be taken on day 3 of iv therapy and limited pharmacokinetic curves on day 7 of iv therapy and/or on day 3 of oral therapy; trough levels will be taken daily after intravenous therapy.

Description:

The pharmacokinetics of fluconazole are expected to be different in ICU patients compared to non-ICU patients and healthy volunteers due to underlying disease(s). Therefore, extrapolation of data from healthy volunteers and non-ICU patients is not possible.

To be able to include 20 patients within the study duration, a multi-centre approach is necessary.

Patients will receive standard care, as stated in the product characteristics or according to local protocols. Blood sampling for pharmacokinetic analysis will be retrieved through a central venous catheter. A maximum of 62 milliliter blood in total will be drawn for this study. Patients will be monitored daily during the treatment period for adverse events of the study drug.

Full pharmacokinetic curves will be taken on day 3 of iv therapy. Limited pharmacokinetic curves will be taken on day 7 of iv therapy. These two moments of pharmacokinetic analysis will enable the determination steady state and enable the determination of intra-individual variability.

As probably not all patients included will be treated with iv fluconazole for 7 days, switching to oral/enteral therapy is allowed after day 3. To assess bioavailability limited pharmacokinetic curves will be taken on day 3 of oral/enteral therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. Subject is managed with a central venous or arterial catheter

Exclusion Criteria:

1. Is known to be hypersensitive to azole antifungal agents

2. Documented history of sensitivity to medicinal products or excipients similar to those found in the fluconazole preparation

3. Has previously participated in this trial

Related Conditions & MeSH terms

• Candidiasis
• Invasive Fungal Infections

Intervention

Drug:
• fluconazole
Dose according to summary of product characteristics (SPC) or local protocols

Locations

Country	Name	City	State
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Radboud university medical center	Nijmegen
Netherlands	University Medical Center Utrecht	Utrecht

Sponsors (1)

Lead Sponsor	Collaborator
Radboud University

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Muilwijk EW, de Lange DW, Schouten JA, Wasmann RE, Ter Heine R, Burger DM, Colbers A, Haas PJ, Verweij PE, Pickkers P, Brüggemann RJ. Suboptimal Dosing of Fluconazole in Critically Ill Patients: Time To Rethink Dosing. Antimicrob Agents Chemother. 2020 Se — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the curve	Full pharmacokinetic curves will be taken op Day 3 and Day 7 (fluconazole).	Days 3 and 7
Secondary	body weight	Identifying influence of body weight on the pharmacokinetics of fluconazole.	Days 3 and 7