Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by Duke University
Sponsor:
Information provided by (Responsible Party):
Kevin Watt, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT01666769
First received: August 14, 2012
Last updated: March 17, 2014
Last verified: August 2013
  Purpose

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


Condition Intervention Phase
Invasive Candidiasis
Drug: Micafungin
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Pharmacokinetics of Micafungin in Children Supported With Extracorporeal Membrane Oxygenation

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Clearance rate (CL), Volume of distribution (V), Oxygenator extraction efficacy


Secondary Outcome Measures:
  • Safety [ Time Frame: From Dose 1 until 7 days after the last dose ] [ Designated as safety issue: Yes ]
    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)


Estimated Enrollment: 50
Study Start Date: January 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Treatment Dosing
Age group: 0 - <2y, Micafungin 8 mg/kg/day IV
Drug: Micafungin
8 mg/kg/day
Other Name: Mycamine
Prophylaxis dosing
Age group: 0-<2y, Micafungin 4 mg/kg/day IV
Drug: Micafungin
4 mg/kg/day
Other Name: Mycamine
Standard of care Dosing
Age group: 2-17.85 y, Micafungin standard of care dosing (decided by treating physician)
Drug: Micafungin
Standard of care Dosing
Other Name: Mycamine

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.

  Eligibility

Ages Eligible for Study:   up to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01666769

Contacts
Contact: Julie Autmizguine, MD 919-668-7817 julie.autmizguine@dm.duke.edu
Contact: Kevin Watt, MD 919-970-8746 kevin.watt@duke.edu

Locations
United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Julie Autmizguine, MD    919-668-7817    julie.autmizguine@dm.duke.edu   
Sub-Investigator: Julie Autmizguine, MD         
Principal Investigator: Kevin Watt, MD         
Sponsors and Collaborators
Kevin Watt
Investigators
Principal Investigator: Kevin Watt, MD Duke Clinical Research Institute
  More Information

No publications provided

Responsible Party: Kevin Watt, Assistant Professor, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT01666769     History of Changes
Other Study ID Numbers: Pro00039552
Study First Received: August 14, 2012
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Duke University:
Extracorporeal membrane oxygenation
ECMO
Extracorporeal life support
Micafungin
Mycamine
Pharmacokinetics

Additional relevant MeSH terms:
Candidiasis
Candidiasis, Invasive
Mycoses
Micafungin
Echinocandins
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014