Evaluating the Conversion of Caspofungin to Micafungin as Empiric Antifungal Therapy in Patients With Persistent Fever and Neutropenia - Full Text View

Sponsors and Collaborators:	Brigham and Women's Hospital Astellas Pharma US, Inc.
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00723073

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 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. In November 2006 the Pharmacy and Therapeutics Committee at BWH/DFCI switched from caspofungin to micafungin as our formulary echinocandin. We plan to evaluate the safety, efficacy, and economic impact of switching from caspofungin to micafungin at our institution for empiric antifungal therapy in febrile neutropenia.

Condition
Febrile Neutropenia

MedlinePlus related topics: Fever

Drug Information available for: Clotrimazole Miconazole Miconazole nitrate Tioconazole Micafungin FK 463 Caspofungin Caspofungin Acetate

U.S. FDA Resources

Study Type:	Observational
Study Design:	Cohort, Retrospective
Official Title:	Evaluating the Conversion of Caspofungin (CAS) to Micafungin (MIC) as Empiric Antifungal Therapy in Patients With Persistent Fever and Neutropenia

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

Primary Outcome Measures:

Percentage of breakthrough invasive fungal infections in each arm [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Mortality at discharge [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
Neutrophil recovery at discharge [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
Duration of therapy with an echinocandin (caspofungin and micafungin) for febrile neutropenia [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: No ]
Hepatotoxicity measure by LFT abnormalities during and after therapy [ Time Frame: 11/1/2005 - 10/31/2007 ] [ Designated as safety issue: Yes ]

Biospecimen Retention: None Retained

Biospecimen Description:

Enrollment:	334
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 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 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 and Women's Hospital 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: ALT, Total bilirubin, Serum Galactomannan, 1.3-BD Glucan
- 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 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 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

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:

Schuler U, Bammer S, Aulitzky WE, Binder C, Böhme A, Egerer G, Sandherr M, Schwerdtfeger R, Silling G, Wandt H, Glasmacher A, Ehninger G. Safety and efficacy of itraconazole compared to amphotericin B as empirical antifungal therapy for neutropenic fever in patients with haematological malignancy. Onkologie. 2007 Apr;30(4):185-91. Epub 2007 Mar 23.

Toubai T, Tanaka J, Ota S, Shigematsu A, Shono Y, Ibata M, Hashino S, Kondo T, Kakinoki Y, Masauzi N, Kasai M, Iwasaki H, Kurosawa M, Asaka M, Imamura M. Efficacy and safety of micafungin in febrile neutropenic patients treated for hematological malignancies. Intern Med. 2007;46(1):3-9. Epub 2007 Jan 1.

Seibel NL, Schwartz C, Arrieta A, Flynn P, Shad A, Albano E, Keirns J, Lau WM, Facklam DP, Buell DN, Walsh TJ. Safety, tolerability, and pharmacokinetics of Micafungin (FK463) in febrile neutropenic pediatric patients. Antimicrob Agents Chemother. 2005 Aug;49(8):3317-24.

Walsh TJ, Teppler H, Donowitz GR, Maertens JA, Baden LR, Dmoszynska A, Cornely OA, Bourque MR, Lupinacci RJ, Sable CA, dePauw BE. Caspofungin versus liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med. 2004 Sep 30;351(14):1391-402.

Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J; National Institute of Allergy and Infectious Diseases Mycoses Study Group. Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002 Jan 24;346(4):225-34.

Wingard JR, White MH, Anaissie E, Raffalli J, Goodman J, Arrieta A; L Amph/ABLC Collaborative Study Group. A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group. Clin Infect Dis. 2000 Nov;31(5):1155-63. Epub 2000 Nov 7.

Winston DJ, Hathorn JW, Schuster MG, Schiller GJ, Territo MC. A multicenter, randomized trial of fluconazole versus amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am J Med. 2000 Mar;108(4):282-9.

Walsh TJ, Finberg RW, Arndt C, Hiemenz J, Schwartz C, Bodensteiner D, Pappas P, Seibel N, Greenberg RN, Dummer S, Schuster M, Holcenberg JS. Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. National Institute of Allergy and Infectious Diseases Mycoses Study Group. N Engl J Med. 1999 Mar 11;340(10):764-71.

Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ; Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer; Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and hematopoietic stem cell transplants: an international consensus. Clin Infect Dis. 2002 Jan 1;34(1):7-14. Epub 2001 Nov 26.

Responsible Party:	Brigham and Women's Hospital ( David W, Kubiak, PharmD, BCPS / Infectious Disease Clinical Specialist )
Study ID Numbers:	2008-P-000605/1; BWH
Study First Received:	July 24, 2008
Last Updated:	July 25, 2008
ClinicalTrials.gov Identifier:	NCT00723073
Health Authority:	United States: Federal Government

Keywords provided by Brigham and Women's Hospital:

micafungin, caspofungin, febrile neutropenia

Study placed in the following topic categories:

Fever
Neutropenia
Clotrimazole
Hematologic Diseases
Miconazole
Caspofungin

Tioconazole
Agranulocytosis
Leukocyte Disorders
Leukopenia
Granulocytopenia
Micafungin

Additional relevant MeSH terms:

Anti-Infective Agents
Therapeutic Uses
Antifungal Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009