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

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT00723073

Enrollment

323

Registered

2008-07-28

Start date

2008-01-31

Completion date

2008-05-31

Last updated

2010-08-31

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Febrile Neutropenia

Keywords

micafungin, caspofungin, febrile neutropenia

Brief 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.

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

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Lack of an Adverse Drug Event (ADE) Attributable to Echinocandin (EC) Therapy That Led to Discontinuation of Therapy	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
Composite Primary Endpoint: Number of Participants With an Overall Favorable Response to Echinocandin Therapy for Empiric Antifungal Therapy for Persistent Febrile Neutropenia (FN)	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.
Successful Treatment of Any Baseline Invasive Fungal Disease (IFD)	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
Mortality at Hospital Discharge	11/1/2005 - 10/31/2007	We assessed all patients in the study cohort who dischaged from the hospital alive
Absence of Any Breakthrough Invasive Fungal Disease (IFD)	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

Secondary

Measure	Time frame	Description
Duration of Echinocadin Therapy for Persistent Febrile Neutropenia (FN)	11/1/2005 - 10/31/2007	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	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)
Specific Type of Adverse Event That Resulted in Echinocandin (EC) Therapy Discontinuation	11/1/2005 - 10/31/2007	The description of the adverse event that resulted in discontinuation of echinocandin (EC) therapy
Duration of Hospitization	11/1/2005 - 10/31/2007	Median number of days patients were hospitalized during the study period
Duration of Neutropenia	11/1/2005 - 10/31/2007	Median number of days patients were neutropenic during the study period

Countries

United States

Participant flow

Participants by arm

Arm	Count
Caspofungin Arm All patients admitted to BWH/DFCI who received at least 2 doses of caspofungin with an ANC \< 500, for persistent febrile neutropenia from 11/1/2005 - 10/31/2006, as there first antifungal agent.	149
Micafungin Arm All patients admitted to BWH/DFCI who received at least 2 doses of micafungin with an ANC \< 500 for persistent febrile neutropenia from 11/1/2006 - 10/31/2007 as there first antifungal agent	174
Total	323

Baseline characteristics

Characteristic	Micafungin Arm	Total	Caspofungin Arm
Age Continuous	49 years	49 years	49 years
hematopoietic stem cell transplantation status Hematopoietic stem cell transplantation	108 participants	189 participants	81 participants
hematopoietic stem cell transplantation status No - Hematopoietic stem cell transplantation	66 participants	134 participants	68 participants
Patient Weight, kg	80 kilograms	80 kilograms	80 kilograms
Primary Underlying Disease Acute lymphoblastic leukemia	20 participants	29 participants	9 participants
Primary Underlying Disease Acute myelogenous leukemia	82 participants	158 participants	76 participants
Primary Underlying Disease Aplastic anemia	5 participants	8 participants	3 participants
Primary Underlying Disease Chronic myelogenous leukemia	8 participants	14 participants	6 participants
Primary Underlying Disease Hodgkin's lymphoma	12 participants	20 participants	8 participants
Primary Underlying Disease Multiple myeloma	8 participants	14 participants	6 participants
Primary Underlying Disease Myelodysplastic syndrome	7 participants	12 participants	5 participants
Primary Underlying Disease Non-Hodgkin's lymphoma	25 participants	53 participants	28 participants
Primary Underlying Disease other onocological diagnosis	7 participants	15 participants	8 participants
Sex: Female, Male Female	75 Participants	144 Participants	69 Participants
Sex: Female, Male Male	99 Participants	179 Participants	80 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	15 / 149	18 / 174
serious Total, serious adverse events	3 / 149	2 / 174

Outcome results

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