Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation
Primary Purpose
Invasive Candidiasis
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Micafungin
Micafungin
Micafungin
Sponsored by
About this trial
This is an interventional treatment trial for Invasive Candidiasis focused on measuring Extracorporeal membrane oxygenation, ECMO, Extracorporeal life support, Micafungin, Mycamine, Pharmacokinetics
Eligibility Criteria
Inclusion Criteria:
- <= 17.85 years at the time of enrollment.
- Sufficient venous access to permit administration of study medication.
- Supported with either venoarterial (VA) or venovenous (VV) ECMO.
- Availability and willingness of the parent/legal guardian to provide written informed consent.
- For treatment dosing arm: confirmed or suspected infection
Exclusion Criteria:
- Subject with a history of anaphylaxis attributed to an echinocandin.
- Any other concomitant condition, which in the opinion of the investigator would preclude a subject's participation in the study.
- Previous participation in this study.
- Pregnancy
Sites / Locations
- Duke University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Other
Other
Other
Arm Label
Treatment Dosing
Prophylaxis dosing
Standard of care Dosing
Arm Description
Age group: 0 - <2y, Micafungin 8 mg/kg/day IV
Age group: 0-<2y, Micafungin 4 mg/kg/day IV
Age group: 2-17.85 y, Micafungin standard of care dosing (decided by treating physician)
Outcomes
Primary Outcome Measures
Pharmacokinetic primary endpoints
Clearance rate (CL), Volume of distribution (V), Oxygenator extraction efficacy
Secondary Outcome Measures
Safety
Number of adverse events (any untoward medical occurrence in humans, whether or not considered drug-related, which occurs during the conduct of a clinical trial)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01666769
Brief Title
Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation
Official Title
Safety and Pharmacokinetics of Micafungin in Children Supported With Extracorporeal Membrane Oxygenation
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
January 2013 (Actual)
Primary Completion Date
February 2, 2016 (Actual)
Study Completion Date
February 9, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Kevin Watt
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Determine proper dosing of micafungin in children supported with extracorporeal membrane oxygenation (ECMO).
Detailed Description
Extracorporeal membrane oxygenation (ECMO) is a cardiopulmonary bypass device that provides life-saving, complete respiratory and cardiac support for children who suffer refractory heart or lung failure. While on ECMO, children are at increased risk of infection, including fungal infection. Antifungal prophylaxis can potentially reduce the burden of disease in children on ECMO. Because fungal infections can result in biofilms that are difficult to treat, treatment includes not only antifungal medications but also removal of any large intravenous lines. However, catheter removal for children on ECMO is impossible; therefore, therapy relies upon optimal antifungal management alone.
Micafungin is an antifungal medication that works well against the most common fungal infections and has been shown to be safe in children. Micafungin may be particularly efficacious in children on ECMO because of the drug's ability to penetrate biofilms. However, the ECMO circuit is known to substantially alter drug levels for many drugs, resulting in important dosing changes. Appropriate micafungin dosing in this setting is unknown and sub-optimal dosing might result in therapeutic and prophylactic failure.
Standard dosing of micafungin are 4 and 2 mg per kilogram of body weight given intravenously once daily for treatment and prophylaxis, respectively. Based on preliminary data and modeling from other studies, investigators hypothesize that 8 and 4 mg per kilogram given once daily will achieve proper drug levels to respectively treat and prevent fungal infections in children under 2 years of age who are supported by ECMO. Because the ECMO circuit should have less of an impact on volume of distribution in larger children, investigators hypothesize that in children from 2 to 18 years old, standard dosing of micafungin will achieve proper drug concentrations.
Investigators hold the FDA investigational new drug application (IND #115255) to give micafungin to children on ECMO at the doses described above. Blood samples will be collected at specific times around the first and fourth micafungin doses to describe the pharmacokinetics and drug extraction by the ECMO circuit.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Invasive Candidiasis
Keywords
Extracorporeal membrane oxygenation, ECMO, Extracorporeal life support, Micafungin, Mycamine, Pharmacokinetics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment Dosing
Arm Type
Other
Arm Description
Age group: 0 - <2y, Micafungin 8 mg/kg/day IV
Arm Title
Prophylaxis dosing
Arm Type
Other
Arm Description
Age group: 0-<2y, Micafungin 4 mg/kg/day IV
Arm Title
Standard of care Dosing
Arm Type
Other
Arm Description
Age group: 2-17.85 y, Micafungin standard of care dosing (decided by treating physician)
Intervention Type
Drug
Intervention Name(s)
Micafungin
Other Intervention Name(s)
Mycamine
Intervention Description
4 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Micafungin
Other Intervention Name(s)
Mycamine
Intervention Description
8 mg/kg/day
Intervention Type
Drug
Intervention Name(s)
Micafungin
Other Intervention Name(s)
Mycamine
Intervention Description
Standard of care Dosing
Primary Outcome Measure Information:
Title
Pharmacokinetic primary endpoints
Description
Clearance rate (CL), Volume of distribution (V), Oxygenator extraction efficacy
Time Frame
Around the first and fourth doses of micafungin: 0-4h prior to and 0-30 min, 60-90 min, 2-4h, 8-10h, 12-16h, 22-24h after infusion of study drug
Secondary Outcome Measure Information:
Title
Safety
Description
Number of adverse events (any untoward medical occurrence in humans, whether or not considered drug-related, which occurs during the conduct of a clinical trial)
Time Frame
From Dose 1 until 7 days after the last dose
10. Eligibility
Sex
All
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
<= 17.85 years at the time of enrollment.
Sufficient venous access to permit administration of study medication.
Supported with either venoarterial (VA) or venovenous (VV) ECMO.
Availability and willingness of the parent/legal guardian to provide written informed consent.
For treatment dosing arm: confirmed or suspected infection
Exclusion Criteria:
Subject with a history of anaphylaxis attributed to an echinocandin.
Any other concomitant condition, which in the opinion of the investigator would preclude a subject's participation in the study.
Previous participation in this study.
Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kevin Watt, MD
Organizational Affiliation
Duke Clinical Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation
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