Pharmacokinetics of Micafungin in Children on Extracorporeal Membrane Oxygenation

NCT ID: NCT01666769

Last Updated: 2019-11-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2016-02-09

Brief Summary

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

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.

Conditions

Invasive Candidiasis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Dosing

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

Group Type: OTHER

Micafungin

Intervention Type: DRUG

8 mg/kg/day

Prophylaxis dosing

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

Group Type: OTHER

Micafungin

Intervention Type: DRUG

4 mg/kg/day

Standard of care Dosing

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

Group Type: OTHER

Micafungin

Intervention Type: DRUG

Standard of care Dosing

Interventions

Micafungin

4 mg/kg/day

Intervention Type: DRUG

Micafungin

8 mg/kg/day

Intervention Type: DRUG

Micafungin

Standard of care Dosing

Intervention Type: DRUG

Other Intervention Names

Mycamine; Mycamine; Mycamine

Eligibility 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

• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kevin Watt

OTHER

Sponsor Role: lead

Responsible Party

Kevin Watt

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Kevin Watt, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Clinical Research Institute

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

Pro00039552

Identifier Type: -

Identifier Source: org_study_id