Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation

Kevin Watt

Status and phase: Completed; Phase 1

Conditions: Invasive Candidiasis

Treatments: Drug: Micafungin

Study type: Interventional

Funder types: Other

Identifiers

NCT01666769

Pro00039552

Details and patient eligibility

About

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

Full 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.

Enrollment: 18 patients

Sex: All

Ages: Under 18 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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18 participants in 3 patient groups

Treatment Dosing

Other group

Description:

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

Treatment:

Drug: Micafungin

Drug: Micafungin

Drug: Micafungin

Prophylaxis dosing

Other group

Description:

Age group: 0-\<2y, Micafungin 4 mg/kg/day IV

Treatment:

Drug: Micafungin

Drug: Micafungin

Drug: Micafungin

Standard of care Dosing

Other group

Description:

Age group: 2-17.85 y, Micafungin standard of care dosing (decided by treating physician)

Treatment:

Drug: Micafungin

Drug: Micafungin

Drug: Micafungin