Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation

Sponsor

Kevin Watt (Other)

Overall Status

Completed

CT.gov ID

NCT01666769

Collaborator

(none)

Enrollment

Location

Arms

37.3

Actual Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Invasive Candidiasis	Drug: Micafungin Drug: Micafungin Drug: Micafungin	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 1, 2013

Actual Primary Completion Date :

Feb 2, 2016

Actual Study Completion Date :

Feb 9, 2016

Arms and Interventions

Arm	Intervention/Treatment
Other: Treatment Dosing Age group: 0 - <2y, Micafungin 8 mg/kg/day IV	Drug: Micafungin 8 mg/kg/day 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
Other: 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 Names: Mycamine

Arm

Intervention/Treatment

Other: Treatment Dosing

Age group: 0 - <2y, Micafungin 8 mg/kg/day IV

Drug: Micafungin

8 mg/kg/day

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

Other: 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 Names:

Mycamine

Outcome Measures

Primary Outcome Measures

Pharmacokinetic primary endpoints [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

Secondary Outcome Measures

Safety [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)

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 18 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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