Clinical trial NCT00839540: Comparison of Candida Eradication and Serum Cidal Activity of Echinocandins
Official title: Comparison of Candida Eradication and Serum Cidal Activity of Echinocandins in Patients With Presumptive Candidemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Candidemia
Keywords: candidemia
echinocandin
micafungin
caspofungin
Lead sponsor: Michigan State University
Sponsor class: OTHER
Collaborators: name: Astellas Pharma US, Inc.
First posted: 2009-02-09
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum Cidal Activity as Tested Against Various Candida Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth)
timeFrame: Pre-treatment, 1.5 hour (h), 12 h and 24 h after receiving the drug
Secondary outcomes:
Other outcomes:
Locations:
city: Lansing
country: United States
facility: Sparrow Hospital
state: Michigan
Study officials:
affiliation: Michigan State University
name: Gary E Stein, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References: