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

Febrile Neutropenia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00723073
• Other study ID #: 2008-P-000605/1; BWH
• Status: Completed
• Phase: N/A
• First received: July 24, 2008
• Last updated: August 25, 2010
• Start date: January 2008
• Est. completion date: May 2008

Study information

• Verified date: August 2010
• Source: Brigham and Women's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 323
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Febrile Neutropenia
• Fever
• Neutropenia

Locations

Country	Name	City	State
United States	Brigham and Women's Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	Astellas Pharma US, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (18)

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Primary Endpoint: Number of Participants With an Overall Favorable Response to Echinocandin Therapy for Empiric Antifungal Therapy for Persistent Febrile Neutropenia (FN)	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	No
Primary	Successful Treatment of Any Baseline Invasive Fungal Disease (IFD)	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	No
Primary	Mortality at Hospital Discharge	We assessed all patients in the study cohort who dischaged from the hospital alive	11/1/2005 - 10/31/2007	No
Primary	Absence of Any Breakthrough Invasive Fungal Disease (IFD)	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	No
Primary	Lack of an Adverse Drug Event (ADE) Attributable to Echinocandin (EC) Therapy That Led to Discontinuation of Therapy	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	No
Secondary	Duration of Echinocadin Therapy for Persistent Febrile Neutropenia (FN)	median duration of therapy with an echinocandin (caspofungin or micafungin) for persistent febrile neutropenia (FN)	11/1/2005 - 10/31/2007	No
Secondary	Liver Function Tests (LFTs) Elevated During or After Echinocandin Therapy	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	No
Secondary	Specific Type of Adverse Event That Resulted in Echinocandin (EC) Therapy Discontinuation	The description of the adverse event that resulted in discontinuation of echinocandin (EC) therapy	11/1/2005 - 10/31/2007	Yes
Secondary	Duration of Hospitization	Median number of days patients were hospitalized during the study period	11/1/2005 - 10/31/2007	No
Secondary	Duration of Neutropenia	Median number of days patients were neutropenic during the study period	11/1/2005 - 10/31/2007	No