Pharmacokinetics/Pharmacodynamics (PK/PD) of Fluconazole in Children on Extracorporeal Membrane Oxygenation (ECMO)

Safety and Pharmacokinetics of Fluconazole Prophylaxis in Children Supported With Extracorporeal Membrane Oxygenation

Extracorporeal membrane oxygenation (ECMO) is a form of heart-lung bypass used to support children who suffer heart or lung failure until whatever illness caused that failure can be treated and reversed. While on ECMO, children are at increased risk of infection, including fungal infection. Treatment for fungal infection includes not only antifungal medications but also removal of any large intravenous (IV) lines. Since ECMO requires large IV lines, proper treatment of fungal infections would be difficult if not impossible. The investigators believe that giving prophylactic antifungal medication to all children on ECMO may prevent fungal infections from developing in the first place.

Fluconazole is an antifungal medication that works well against the most common fungal infections and has been shown to be safe in children. Unfortunately, the ECMO machine has the potential to significantly alter the drug levels of medications so the investigators do not know the proper dose of Fluconazole to give children on ECMO. Standard dosing of fluconazole is 12mg per kilogram of body weight given intravenously once daily. Based on preliminary data and modeling from other studies, the investigators think 25mg per kilogram given once weekly will achieve proper drug levels to prevent fungal infections. The investigators have obtained FDA approval to give this dose of fluconazole to children on ECMO who are enrolled in the study. Blood samples will be collected at specific times around the first and second fluconazole doses to describe the PK and drug extraction by the ECMO circuit.

Study Overview

• Status: Completed
• Conditions: Fungal Infection; Cardiopulmonary Arrest
• Intervention / Treatment: Drug: Fluconazole

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. <= 17.5 years at the time of enrollment.
2. Sufficient venous access to permit administration of study medication.
3. Supported with either venoarterial (VA) or venovenous (VV) ECMO.
4. Availability and willingness of the parent/legal guardian to provide written informed consent.

Exclusion Criteria:

1. Subject with a history of anaphylaxis attributed to an azole.
2. Any other concomitant condition, which in the opinion of the investigator would preclude a subject's participation in the study.
3. Previous participation in this study.
4. Subjects who are receiving or who have received cyclosporine, tacrolimus, or azithromycin in the 72 hours prior to first dose of study product require protocol chair notification prior to enrollment.
5. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Fluconazole	Drug: Fluconazole; 25mg/kg intravenously once weekly while on ECMO; Other Names: Diflucan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics/Pharmacodynamics	Determine proper dosing of fluconazole in children supported with extracorporeal membrane oxygentation	Quarterly

Collaborators and Investigators

• Sponsor: Michael Cohen-Wolkowiez
• Investigators: Principal Investigator: Kevin M Watt, MD, Duke University

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (ACTUAL): February 20, 2013
• Study Completion (ACTUAL): February 20, 2013

Study Registration Dates

• First Submitted: July 22, 2010
• First Submitted That Met QC Criteria: July 23, 2010
• First Posted (ESTIMATE): July 26, 2010

Study Record Updates

• Last Update Posted (ACTUAL): November 22, 2017
• Last Update Submitted That Met QC Criteria: November 20, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: pharmacokinetics; ECMO; pharmacodynamics; extracorporeal membrane oxygenation; fluconazole; extracorporeal life support; diflucan
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Infections; Bacterial Infections and Mycoses; Mycoses; Heart Arrest; 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: Pro00022822