Comparison of Candida Eradication and Serum Cidal Activity of Echinocandins

Gary E. Stein, Pharm.D.

Status and phase: Completed; Phase 4

Conditions: Candidemia

Treatments: Drug: micafungin; Drug: Micafungin; Drug: Caspofungin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00839540

PA-07-004

Details and patient eligibility

About

The purpose of this pharmacokinetic (PK) and pharmacodynamic (PD) study is:

To study the rate and duration of serum cidal activity of caspofungin (CFG) and micafungin (MFG) against Candida isolates from the subject and against Candida glabrata with varying degrees of caspofungin susceptibilities.

This investigation will provide clinicians information supporting the use of caspofungin and micafungin in situations where Candida strains may be a cause of infection.

Full description

Methods:

Patients - Adult patients with presumptive candidemia. Patients with severe neutropenia (<500) APACHE II scores > 20, or significant liver disease will be excluded. All will give written informed consent (Pappas et al. CID. Oct 1, 2007).

Drugs - Patients will receive either CFG: 70 mg loading dose (LD) followed by 50 mg once daily (qd) (8 patients), MFG: 100 mg qd (8 patients) or MFG: 200 mg qd (8 patients). All agents will be given by slow IV infusion (MFG will be supplied by Astellas).

Sera - Blood samples will be collected at the end of the infusion (peak) and at 12 h and 24 h (trough) after the beginning of an infusion (day 3-4).

Each patients sera will be tested (MIC and cidal activity) against their own Candida isolate (if isolated). In addition, recent clinical isolates of C. glabrata will also be tested against patient sera (time-kill) to verify previous in vitro and animal PD studies (Cota. AAC. Nov. 2006; Wiederhold. AAC. May 2007).

Results:

• Patient outcome, including Candida eradication, will be documented for each patient by repeat culture.
• Serum concentrations (lab to be determined) and PK analysis of each echinocandin will be determined for each patient.
• Serum cidal titers will be measured against each of the Candida isolates for each agent at each time period. Median and geometric mean Peak and duration of cidal activity will then be determined and compared.

Enrollment: 21 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Adult patients with presumptive candidemia

Exclusion criteria

• Patients with severe neutropenia (<500)
• Patients with APACHE II scores > 20
• Patients with severe liver disease

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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21 participants in 3 patient groups

micafungin 100

Active Comparator group

Description:

Patients receive Micafungin 100 mg qd

Treatment:

Drug: micafungin

micafungin 200

Active Comparator group

Description:

Patients receive 200 mg Micafungin qd

Treatment:

Drug: Micafungin

Caspofungin

Active Comparator group

Description:

Patients receive caspofungin 70 mg LD followed by 50 mg qd

Treatment:

Drug: Caspofungin