Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation

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.

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