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

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma US, Inc.
Information provided by:
Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT00723073
First received: July 24, 2008
Last updated: August 25, 2010
Last verified: August 2010
  Purpose

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.


Condition
Febrile Neutropenia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Retrospective
Official Title: Evaluation of Caspofungin or Micafungin as Empiric Antifungal Therapy in Adult Patients With Persistent Febrile Neutropenia: A Retrospective, Observational, Sequential Cohort Analysis

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • Successful Treatment of Any Baseline Invasive Fungal Disease (IFD) [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
    Possible or proven baseline invasive fungal disease were defined as were diagnosed within the 2 days of initiating echinocandin therapy for persistent febrile neutropenia

  • Mortality at Hospital Discharge [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
    We assessed all patients in the study cohort who dischaged from the hospital alive

  • Absence of Any Breakthrough Invasive Fungal Disease (IFD) [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
    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

  • 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 ] [ Designated as safety issue: No ]
    Defined as any advsere event directly attributable to echinocandin treatment that led to discontinuation of therapy or switch to alternative therapy


Secondary Outcome Measures:
  • Duration of Echinocadin Therapy for Persistent Febrile Neutropenia (FN) [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
    median duration of therapy with an echinocandin (caspofungin or micafungin) for persistent febrile neutropenia (FN)

  • Liver Function Tests (LFTs) Elevated During or After Echinocandin Therapy [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
    aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 5x the upper limit of normal (ULN) or total bilirubin > 3x the upper limit of normal (ULN)

  • Specific Type of Adverse Event That Resulted in Echinocandin (EC) Therapy Discontinuation [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: Yes ]
    The description of the adverse event that resulted in discontinuation of echinocandin (EC) therapy

  • Duration of Hospitization [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
    Median number of days patients were hospitalized during the study period

  • Duration of Neutropenia [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
    Median number of days patients were neutropenic during the study period


Enrollment: 323
Study Start Date: January 2008
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Groups/Cohorts
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

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
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00723073

Locations
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Brigham and Women's Hospital
Astellas Pharma US, Inc.
Investigators
Principal Investigator: David W Kubiak, PharmD Brigham and Women's Hospital
  More Information

Publications:

Responsible Party: David W, Kubiak, PharmD, BCPS / Infectious Disease Clinical Specialist, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT00723073     History of Changes
Other Study ID Numbers: 2008-P-000605/1; BWH
Study First Received: July 24, 2008
Results First Received: June 7, 2010
Last Updated: August 25, 2010
Health Authority: United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:
micafungin, caspofungin, febrile neutropenia

Additional relevant MeSH terms:
Fever
Neutropenia
Febrile Neutropenia
Body Temperature Changes
Signs and Symptoms
Agranulocytosis
Leukopenia
Leukocyte Disorders
Hematologic Diseases
Antifungal Agents
Clotrimazole
Miconazole
Caspofungin
Micafungin
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Local
14-alpha Demethylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 27, 2014