Comparison of Candida Eradication and Serum Cidal Activity of Echinocandins

Comparison of Candida Eradication and Serum Cidal Activity of Echinocandins in Patients With Presumptive Candidemia

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.

Study Overview

• Status: Completed
• Conditions: Candidemia
• Intervention / Treatment: Drug: micafungin; Drug: Micafungin; Drug: Caspofungin

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.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Lansing, Michigan, United States, 48912
      • Sparrow Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: micafungin 100; Patients receive Micafungin 100 mg qd	Drug: micafungin; 100 mg qd by slow IV infusion for 24 h; Other Names: Micamine
Active Comparator: micafungin 200; Patients receive 200 mg Micafungin qd	Drug: Micafungin; 200 mg qd by slow IV infusion for 24 h; Other Names: Micamine
Active Comparator: Caspofungin; Patients receive caspofungin 70 mg LD followed by 50 mg qd	Drug: Caspofungin; 70 mg LD followed by 50 mg qd by slow IV infusion for 24 h; Other Names: Cancidas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Cidal Activity as Tested Against Various Candida Isolates and Reported as Ex-vivo Effect (Log Inhibition of Growth)	Serum cidal activity of serum collected at different timepoints from the patients will be tested against various Candida isolates and the ex-vivo effect reported as log inhibition (logrithmic measurement of the decrease in microbiological growth). These Candida isolates had a range of minimum inhibitory concentrations (MIC) to Caspofungin (C) and Micafungin (M).	Pre-treatment, 1.5 hour (h), 12 h and 24 h after receiving the drug

Collaborators and Investigators

• Sponsor: Gary E. Stein, Pharm.D.
• Collaborators: Astellas Pharma US, Inc.
• Investigators: Principal Investigator: Gary E Stein, Pharm.D., Michigan State University

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): May 1, 2010
• Study Completion (Actual): May 1, 2010

Study Registration Dates

• First Submitted: February 6, 2009
• First Submitted That Met QC Criteria: February 6, 2009
• First Posted (Estimated): February 9, 2009

Study Record Updates

• Last Update Posted (Actual): April 30, 2024
• Last Update Submitted That Met QC Criteria: April 27, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: candidemia; caspofungin; micafungin; echinocandin
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Bacterial Infections and Mycoses; Sepsis; Mycoses; Invasive Fungal Infections; Fungemia; Candidiasis; Candidiasis, Invasive; Candidemia; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antifungal Agents; Micafungin; Caspofungin
• Other Study ID Numbers: PA-07-004