Caspofungin or Micafungin as Empiric Antifungal Therapy for Persistent Fever and Neutropenia

August 25, 2010 updated by: Brigham and Women's Hospital

Evaluation of Caspofungin or Micafungin as Empiric Antifungal Therapy in Adult Patients With Persistent Febrile Neutropenia: A Retrospective, Observational, Sequential Cohort Analysis

Invasive fungal infections are an important cause of morbidity and mortality in patients with neutropenia who are receiving chemotherapy for cancer. Early diagnosis of these infections is difficult and fever may be the only sign. A delay in treatment while a diagnosis is pursued may lead to increased morbidity and mortality. There are now several echinocandins available with similar in vitro spectrum of activity. Caspofungin is the only echinocandin Food and Drug Administration (FDA) approved for empiric antifungal therapy in febrile neutropenia. Although all echinocandin antifungal agents have similar spectrum of activity, there are limited data on the use of micafungin in patients with persistent fever and neutropenia (FN). In November 2006 the Pharmacy and Therapeutics Committee at Brigham & Women's Hospital / Dana Farber Cancer Institute (BWH/DFCI) switched from caspofungin to micafungin as our formulary echinocandin. Given the limited clinical data on the use of micafungin as empiric antifungal therapy in patients with FN, we sought to evaluate the safety and effectiveness of micafungin, compared with caspofungin, for this indication using a sequential cohort analysis of patients treated before and after the formulary change at Brigham and Women's Hospital.

Study Overview

Status

Completed

Conditions

Detailed Description

Objectives

This retrospective cohort analysis of converting from caspofungin to micafungin as empiric antifungal therapy for cancer patients who are persistently febrile and neutropenic after receiving broad spectrum antibiotics at Brigham & Women's Hospital / Dana Farber Cancer Institute (BWH/DFCI) is designed to evaluate the following objectives:

  • Safety of micafungin in this patient population
  • Effective dose of 100 mg daily of micafungin compared to 70mg x1, then 50 mg daily of caspofungin
  • Economic impact of converting or formulary echinocandin from micafungin to caspofungin

Study Design

  • Retrospective cohort analysis - limited to medical records

  • Data to be collected include the following:

    • Demographic information: including: gender, age, race
    • Past medical history and admitting diagnoses
    • Laboratory results: Liver function tests (LFTs), Including alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total bilirubin, as well as serum fungal assays: Serum Galactomannan assay, 1.3-BD Glucan assay
    • Concomitant medications and duration of therapy for all systemic: antibiotics and antifungals
    • All invasive breakthrough fungal infection details, including speciation and outcomes during echinocandin therapy
    • Dosing, duration, and adverse events associated with echinocandin therapy

Study Type

Observational

Enrollment (Actual)

323

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Brigham and Women's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Cancer patients who are persistently febrile and neutropenic after receiving broad spectrum antibiotics and receive empiric antifungal therapy with either caspofungin or micafungin

Description

Inclusion Criteria:

  • All patients admitted to BWH/DFCI who received at least 2 doses of caspofungin with an Absolute Neutrophil Count (ANC) < 500, for persistent febrile neutropenia from 11/1/2005 - 10/31/2006, as there first antifungal agent.
  • All patients admitted to BWH/DFCI who received at least 2 doses of micafungin with an Absolute Neutrophil Count (ANC) < 500 for persistent febrile neutropenia from 11/1/2006 - 10/31/2007 as there first antifungal agent

Exclusion Criteria:

  • Patients receiving an echinocandin antifungal agent (micafungin or caspofungin) for an indication other then empiric therapy in febrile neutropenia
  • Patients receiving therapy for an active or on-going invasive fungal infection
  • Patients who received both caspofungin and micafungin during the same admission
  • Patients with an ANC > 500 at when either micafungin or caspofungin was started
  • Patients who received another antifungal agent for persistent febrile neutropenia, e.g., voriconazole, amphotericin B liposome, posaconazole, etc... Before they received an echinocandin (caspofungin or micafungin) will be excluded

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Caspofungin arm
All patients admitted to BWH/DFCI who received at least 2 doses of caspofungin with an Absolute Neutrophil Count (ANC) < 500, for persistent febrile neutropenia from 11/1/2005 - 10/31/2006, as there first antifungal agent.
Micafungin arm
All patients admitted to BWH/DFCI who received at least 2 doses of micafungin with an Absolute Neutrophil Count (ANC) < 500 for persistent febrile neutropenia from 11/1/2006 - 10/31/2007 as there first antifungal agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Composite Primary Endpoint: Number of Participants With an Overall Favorable Response to Echinocandin Therapy for Empiric Antifungal Therapy for Persistent Febrile Neutropenia (FN)
Time Frame: 11/1/2005 - 10/31/2007
Overall favorable response was defined as achievement of successful treatment of baseline fungal infections, survival to hospital discharge, absence of breakthrough Ivasive fungal disese (IFD), and lack of advserse events (AE) attributable to treatment that led to discontinuation of echinocandin therapy.
11/1/2005 - 10/31/2007
Successful Treatment of Any Baseline Invasive Fungal Disease (IFD)
Time Frame: 11/1/2005 - 10/31/2007
Possible or proven baseline invasive fungal disease were defined as were diagnosed within the 2 days of initiating echinocandin therapy for persistent febrile neutropenia
11/1/2005 - 10/31/2007
Mortality at Hospital Discharge
Time Frame: 11/1/2005 - 10/31/2007
We assessed all patients in the study cohort who dischaged from the hospital alive
11/1/2005 - 10/31/2007
Absence of Any Breakthrough Invasive Fungal Disease (IFD)
Time Frame: 11/1/2005 - 10/31/2007
a breakthrough invasive fungal disesase was defined as any fungal infection that was diagnosed > 3 days on or during therapy or within 7 days after completion of therapy with an echinocandin
11/1/2005 - 10/31/2007
Lack of an Adverse Drug Event (ADE) Attributable to Echinocandin (EC) Therapy That Led to Discontinuation of Therapy
Time Frame: 11/1/2005 - 10/31/2007
Defined as any advsere event directly attributable to echinocandin treatment that led to discontinuation of therapy or switch to alternative therapy
11/1/2005 - 10/31/2007

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Echinocadin Therapy for Persistent Febrile Neutropenia (FN)
Time Frame: 11/1/2005 - 10/31/2007
median duration of therapy with an echinocandin (caspofungin or micafungin) for persistent febrile neutropenia (FN)
11/1/2005 - 10/31/2007
Liver Function Tests (LFTs) Elevated During or After Echinocandin Therapy
Time Frame: 11/1/2005 - 10/31/2007
aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 5x the upper limit of normal (ULN) or total bilirubin > 3x the upper limit of normal (ULN)
11/1/2005 - 10/31/2007
Specific Type of Adverse Event That Resulted in Echinocandin (EC) Therapy Discontinuation
Time Frame: 11/1/2005 - 10/31/2007
The description of the adverse event that resulted in discontinuation of echinocandin (EC) therapy
11/1/2005 - 10/31/2007
Duration of Hospitization
Time Frame: 11/1/2005 - 10/31/2007
Median number of days patients were hospitalized during the study period
11/1/2005 - 10/31/2007
Duration of Neutropenia
Time Frame: 11/1/2005 - 10/31/2007
Median number of days patients were neutropenic during the study period
11/1/2005 - 10/31/2007

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Brigham and Women's Hospital

Collaborators

Astellas Pharma US, Inc.

Investigators

  • Principal Investigator: David W Kubiak, PharmD, Brigham and Women's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (ACTUAL)

May 1, 2008

Study Completion (ACTUAL)

May 1, 2008

Study Registration Dates

First Submitted

July 24, 2008

First Submitted That Met QC Criteria

July 25, 2008

First Posted (ESTIMATE)

July 28, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

August 31, 2010

Last Update Submitted That Met QC Criteria

August 25, 2010

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2008-P-000605/1; BWH

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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