Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation

November 1, 2019 updated by: Kevin Watt

Safety and Pharmacokinetics of Micafungin in Children Supported With Extracorporeal Membrane Oxygenation

Determine proper dosing of micafungin in children supported with extracorporeal membrane oxygenation (ECMO).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 14 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Treatment Dosing
Age group: 0 - <2y, Micafungin 8 mg/kg/day IV
Drug: Micafungin
4 mg/kg/day
Other Names:
  • Mycamine
Drug: Micafungin
8 mg/kg/day
Other Names:
  • Mycamine
Drug: Micafungin
Standard of care Dosing
Other Names:
  • Mycamine
Other: Prophylaxis dosing
Age group: 0-<2y, Micafungin 4 mg/kg/day IV
Drug: Micafungin
4 mg/kg/day
Other Names:
  • Mycamine
Drug: Micafungin
8 mg/kg/day
Other Names:
  • Mycamine
Drug: Micafungin
Standard of care Dosing
Other Names:
  • Mycamine
Other: Standard of care Dosing
Age group: 2-17.85 y, Micafungin standard of care dosing (decided by treating physician)
Drug: Micafungin
4 mg/kg/day
Other Names:
  • Mycamine
Drug: Micafungin
8 mg/kg/day
Other Names:
  • Mycamine
Drug: Micafungin
Standard of care Dosing
Other Names:
  • Mycamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetic primary endpoints
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
Clearance rate (CL), Volume of distribution (V), Oxygenator extraction efficacy
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 Measures

Outcome Measure
Measure Description
Time Frame
Safety
Time Frame: From Dose 1 until 7 days after the last dose
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)
From Dose 1 until 7 days after the last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Kevin Watt

Investigators

  • Principal Investigator: Kevin Watt, MD, Duke Clinical Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2013

Primary Completion (Actual)

February 2, 2016

Study Completion (Actual)

February 9, 2016

Study Registration Dates

First Submitted

August 14, 2012

First Submitted That Met QC Criteria

August 14, 2012

First Posted (Estimate)

August 16, 2012

Study Record Updates

Last Update Posted (Actual)

November 5, 2019

Last Update Submitted That Met QC Criteria

November 1, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00039552

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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