Pharmacokinetics of Fluconazole IV as Prophylaxis or Therapy to ICU Patients (PACIFIC)

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

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.

Study Overview

• Status: Completed
• Conditions: Candidiasis
• Intervention / Treatment: Drug: fluconazole

Detailed 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.

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

Contacts and Locations

Study Locations

• Netherlands
  • Nijmegen, Netherlands
    • Radboud University Medical Center
  • Nijmegen, Netherlands
    • Canisius Wilhelmina Ziekenhuis
  • Utrecht, Netherlands
    • University Medical Center Utrecht

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 fluconazole as prophylaxis or therapy for an (invasive) fungal infection at the ICU will be included.

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. 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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve	Full pharmacokinetic curves will be taken op Day 3 and Day 7 (fluconazole).	Days 3 and 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
body weight	Identifying influence of body weight on the pharmacokinetics of fluconazole.	Days 3 and 7

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Publications and helpful links

General Publications

• Muilwijk EW, de Lange DW, Schouten JA, Wasmann RE, Ter Heine R, Burger DM, Colbers A, Haas PJ, Verweij PE, Pickkers P, Bruggemann RJ. Suboptimal Dosing of Fluconazole in Critically Ill Patients: Time To Rethink Dosing. Antimicrob Agents Chemother. 2020 Sep 21;64(10):e00984-20. doi: 10.1128/AAC.00984-20. Print 2020 Sep 21.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: August 12, 2015
• First Submitted That Met QC Criteria: January 25, 2016
• First Posted (Estimate): January 28, 2016

Study Record Updates

• Last Update Posted (Actual): December 7, 2020
• Last Update Submitted That Met QC Criteria: December 4, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: intensive care unit; candidiasis; pharmacokinetics; invasive fungal infection; fluconazole
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Candidiasis; Invasive Fungal Infections; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Fluconazole
• Other Study ID Numbers: UMCN-AKF14.06