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

History of Changes

Results First Received: June 7, 2010

Study Type:	Observational
Study Design:	Observational Model: Cohort; Time Perspective: Retrospective
Condition:	Febrile Neutropenia

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups

	Description
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

Participant Flow: Overall Study

	Caspofungin Arm	Micafungin Arm
STARTED	149	174
COMPLETED	149	174
NOT COMPLETED	0	0

Baseline Characteristics

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Reporting Groups

	Description
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
Total	Total of all reporting groups

Baseline Measures

	Caspofungin Arm	Micafungin Arm	Total
Number of Participants [units: participants]	149	174	323
Age [units: years] Median ( Inter-Quartile Range )	49 ( 39 to 58 )	49 ( 40 to 58 )	49 ( 39 to 58 )
Gender [units: participants]
Female	69	75	144
Male	80	99	179
Primary Underlying Disease ^[1] [units: participants]
Acute myelogenous leukemia	76	82	158
Non-Hodgkin's lymphoma	28	25	53
Acute lymphoblastic leukemia	9	20	29
Hodgkin's lymphoma	8	12	20
Chronic myelogenous leukemia	6	8	14
Multiple myeloma	6	8	14
Myelodysplastic syndrome	5	7	12
Aplastic anemia	3	5	8
other onocological diagnosis	8	7	15
hematopoietic stem cell transplantation status [units: participants]
Hematopoietic stem cell transplantation	81	108	189
No - Hematopoietic stem cell transplantation	68	66	134
Patient Weight, kg [units: kilograms] Median ( Inter-Quartile Range )	80 ( 67 to 89 )	80 ( 65 to 95 )	80 ( 65 to 95 )

[1]	primary oncological diagnosis

Outcome Measures

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1. Primary:

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 ]

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2. Primary:

Successful Treatment of Any Baseline Invasive Fungal Disease (IFD) [ Time Frame: 11/1/2005 - 10/31/2007 ]

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3. Primary:

Mortality at Hospital Discharge [ Time Frame: 11/1/2005 - 10/31/2007 ]

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4. Primary:

Absence of Any Breakthrough Invasive Fungal Disease (IFD) [ Time Frame: 11/1/2005 - 10/31/2007 ]

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5. Primary:

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 ]

Show Outcome Measure 5

6. Secondary:

Duration of Echinocadin Therapy for Persistent Febrile Neutropenia (FN) [ Time Frame: 11/1/2005 - 10/31/2007 ]

Show Outcome Measure 6

7. Secondary:

Liver Function Tests (LFTs) Elevated During or After Echinocandin Therapy [ Time Frame: 11/1/2005 - 10/31/2007 ]

Show Outcome Measure 7

8. Secondary:

Specific Type of Adverse Event That Resulted in Echinocandin (EC) Therapy Discontinuation [ Time Frame: 11/1/2005 - 10/31/2007 ]

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9. Secondary:

Duration of Hospitization [ Time Frame: 11/1/2005 - 10/31/2007 ]

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10. Secondary:

Duration of Neutropenia [ Time Frame: 11/1/2005 - 10/31/2007 ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Retrospective, observational, sequential cohort study conducted at a single center. Only adult patients were treated at our institution, so these results cannot be extrapolated to a pediatric population.

Results Point of Contact:

Name/Title: David Kubiak, Principle Investigator
Organization: Brigham and Women's Hospital
phone: 617-525-8417
e-mail: dwkubiak@partners.org

Publications of Results:

Kubiak DW, Bryar JM, McDonnell AM, Delgado-Flores JO, Mui E, Baden LR, Marty FM. Evaluation of caspofungin or micafungin as empiric antifungal therapy in adult patients with persistent febrile neutropenia: a retrospective, observational, sequential cohort analysis. Clin Ther. 2010 Apr;32(4):637-48.

Other 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.

Hughes WT, Armstrong D, Bodey GP, Bow EJ, Brown AE, Calandra T, Feld R, Pizzo PA, Rolston KV, Shenep JL, Young LS. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis. 2002 Mar 15;34(6):730-51. Epub 2002 Feb 13. No abstract available.

Vartivarian SE, Anaissie EJ, Bodey GP. Emerging fungal pathogens in immunocompromised patients: classification, diagnosis, and management. Clin Infect Dis. 1993 Nov;17 Suppl 2:S487-91. Review.

Perfect JR, Dodds Ashley E, Drew R. Design of aerosolized amphotericin b formulations for prophylaxis trials among lung transplant recipients. Clin Infect Dis. 2004 Oct 15;39 Suppl 4:S207-10.

Pfaller MA, Boyken L, Hollis RJ, Kroeger J, Messer SA, Tendolkar S, Diekema DJ. In vitro susceptibility of invasive isolates of Candida spp. to anidulafungin, caspofungin, and micafungin: six years of global surveillance. J Clin Microbiol. 2008 Jan;46(1):150-6. Epub 2007 Nov 21. Erratum in: J Clin Microbiol. 2008 Sep;46(9):3184-5.

Kuse ER, Chetchotisakd P, da Cunha CA, Ruhnke M, Barrios C, Raghunadharao D, Sekhon JS, Freire A, Ramasubramanian V, Demeyer I, Nucci M, Leelarasamee A, Jacobs F, Decruyenaere J, Pittet D, Ullmann AJ, Ostrosky-Zeichner L, Lortholary O, Koblinger S, Diekmann-Berndt H, Cornely OA; Micafungin Invasive Candidiasis Working Group. Micafungin versus liposomal amphotericin B for candidaemia and invasive candidosis: a phase III randomised double-blind trial. Lancet. 2007 May 5;369(9572):1519-27.

Yanada M, Kiyoi H, Murata M, Suzuki M, Iwai M, Yokozawa T, Baba H, Emi N, Naoe T. Micafungin, a novel antifungal agent, as empirical therapy in acute leukemia patients with febrile neutropenia. Intern Med. 2006;45(5):259-64. Epub 2006 Apr 3.

Pappas PG, Rotstein CM, Betts RF, Nucci M, Talwar D, De Waele JJ, Vazquez JA, Dupont BF, Horn DL, Ostrosky-Zeichner L, Reboli AC, Suh B, Digumarti R, Wu C, Kovanda LL, Arnold LJ, Buell DN. Micafungin versus caspofungin for treatment of candidemia and other forms of invasive candidiasis. Clin Infect Dis. 2007 Oct 1;45(7):883-93. Epub 2007 Aug 29. Erratum in: Clin Infect Dis. 2008 Jul 15;47(2):302.

Sucher AJ, Chahine EB, Balcer HE. Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. Epub 2009 Sep 1. Review.

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

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