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

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00723073
• Collaborator: Astellas Pharma US, Inc. (Industry)
• Enrollment: 323
• Location: 1
• Duration (Months): 4
• Patients Per Site Per Month: 81.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Febrile Neutropenia

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

Study Design

• Study Type: Observational
• Actual Enrollment: 323 participants
• 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
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: May 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

3. Mortality at Hospital Discharge [11/1/2005 - 10/31/2007]

   We assessed all patients in the study cohort who dischaged from the hospital alive

4. 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

5. 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

Secondary Outcome Measures

1. 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)

2. 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)

3. 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

4. Duration of Hospitization [11/1/2005 - 10/31/2007]

   Median number of days patients were hospitalized during the study period

5. Duration of Neutropenia [11/1/2005 - 10/31/2007]

   Median number of days patients were neutropenic during the study period

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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):1519-1527. doi: 10.1016/S0140-6736(07)60605-9.
• 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.
• 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.
• 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.
• 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.
• Sucher AJ, Chahine EB, Balcer HE. Echinocandins: the newest class of antifungals. Ann Pharmacother. 2009 Oct;43(10):1647-57. doi: 10.1345/aph.1M237. Epub 2009 Sep 1. Review.
• 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.
• 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.
• 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.
• 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, Laverdière 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. Erratum in: N Engl J Med. 2007 Feb 15;356(7):760.
• 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.
• 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.
• 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.

• ClinicalTrials.gov Identifier: NCT00723073
• Other Study ID Numbers: 2008-P-000605/1; BWH
• First Posted: Jul 28, 2008
• Last Update Posted: Aug 31, 2010
• Last Verified: Aug 1, 2010

• Keywords provided by , ,: micafungin, caspofungin, febrile neutropenia
• Additional relevant MeSH terms: Neutropenia; Febrile Neutropenia; Hyperthermia; Fever

Study Results

Participant Flow

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Period Title: Overall Study
STARTED	149	174
COMPLETED	149	174
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Caspofungin Arm	Micafungin Arm	Total
Arm/Group Description	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	Total of all reporting groups
Overall Participants	149	174	323
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	49	49	49
Sex: Female, Male (Count of Participants)
Female	69 46.3%	75 43.1%	144 44.6%
Male	80 53.7%	99 56.9%	179 55.4%
Primary Underlying Disease (participants) [Number]
Acute myelogenous leukemia	76 51%	82 47.1%	158 48.9%
Non-Hodgkin's lymphoma	28 18.8%	25 14.4%	53 16.4%
Acute lymphoblastic leukemia	9 6%	20 11.5%	29 9%
Hodgkin's lymphoma	8 5.4%	12 6.9%	20 6.2%
Chronic myelogenous leukemia	6 4%	8 4.6%	14 4.3%
Multiple myeloma	6 4%	8 4.6%	14 4.3%
Myelodysplastic syndrome	5 3.4%	7 4%	12 3.7%
Aplastic anemia	3 2%	5 2.9%	8 2.5%
other onocological diagnosis	8 5.4%	7 4%	15 4.6%
hematopoietic stem cell transplantation status (participants) [Number]
Hematopoietic stem cell transplantation	81 54.4%	108 62.1%	189 58.5%
No - Hematopoietic stem cell transplantation	68 45.6%	66 37.9%	134 41.5%
Patient Weight, kg (kilograms) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [kilograms]	80	80	80

Outcome Measures

1. Primary Outcome

Title	Composite Primary Endpoint: Number of Participants With an Overall Favorable Response to Echinocandin Therapy for Empiric Antifungal Therapy for Persistent Febrile Neutropenia (FN)
Description	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.
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
Yes	122 81.9%	141 81%
No	27 18.1%	33 19%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.10
	Parameter Dispersion	Type: Standard Deviation; Value: 1
	Estimation Comments

2. Primary Outcome

Title	Successful Treatment of Any Baseline Invasive Fungal Disease (IFD)
Description	Possible or proven baseline invasive fungal disease were defined as were diagnosed within the 2 days of initiating echinocandin therapy for persistent febrile neutropenia
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
No Baseline IFD	146 98%	168 96.6%
Successfully treated baseline IFD	2 1.3%	4 2.3%
Unsuccessfully treated baseline IFD	1 0.7%	2 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.0
	Confidence Interval	(2-Sided) 95%; 0.38 to 2.70
	Parameter Dispersion	Type: Standard Deviation; Value: 1
	Estimation Comments

3. Primary Outcome

Title	Mortality at Hospital Discharge
Description	We assessed all patients in the study cohort who dischaged from the hospital alive
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
Alive at hospital discharge	137 91.9%	161 92.5%
Died before hospitial discharge	12 8.1%	13 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.99
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.44 to 1.97
	Parameter Dispersion	Type: Standard Deviation; Value: 1
	Estimation Comments

4. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
No breakthrough IFD	133 89.3%	153 87.9%
Breakthrough IFD	16 10.7%	21 12.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.61 to 2.07
	Parameter Dispersion	Type: Standard Deviation; Value: 1
	Estimation Comments

5. Primary Outcome

Title	Lack of an Adverse Drug Event (ADE) Attributable to Echinocandin (EC) Therapy That Led to Discontinuation of Therapy
Description	Defined as any advsere event directly attributable to echinocandin treatment that led to discontinuation of therapy or switch to alternative therapy
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
No ADE	146 98%	172 98.9%
ADE which caused EC therapy discontinuation	3 2%	2 1.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.10 to 3.37
	Parameter Dispersion	Type: Standard Deviation; Value: 1
	Estimation Comments

6. Secondary Outcome

Title	Duration of Echinocadin Therapy for Persistent Febrile Neutropenia (FN)
Description	median duration of therapy with an echinocandin (caspofungin or micafungin) for persistent febrile neutropenia (FN)
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
Median (Inter-Quartile Range) [days]	10	9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.66
	Comments
	Method	Chi-squared
	Comments

7. Secondary Outcome

Title	Liver Function Tests (LFTs) Elevated During or After Echinocandin Therapy
Description	aspartate aminotransferase (AST) or alanine aminotransferase (ALT)> 5x the upper limit of normal (ULN) or total bilirubin > 3x the upper limit of normal (ULN)
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
No LFT elevations	110 73.8%	132 75.9%
AST > 5x upper limit of normal	14 9.4%	15 8.6%
ALT > 5x upper limit of normal	10 6.7%	9 5.2%
Total Bilirubin >3x upper limit of normal	15 10.1%	18 10.3%

8. Secondary Outcome

Title	Specific Type of Adverse Event That Resulted in Echinocandin (EC) Therapy Discontinuation
Description	The description of the adverse event that resulted in discontinuation of echinocandin (EC) therapy
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
No Adverse Event requiring EC discontinuation	146 98%	172 98.9%
Rash	2 1.3%	1 0.6%
Liver function Test (LFT) increase	0 0%	1 0.6%
Anaphylaxis	1 0.7%	0 0%

9. Secondary Outcome

Title	Duration of Hospitization
Description	Median number of days patients were hospitalized during the study period
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
Median (Inter-Quartile Range) [days]	29	28

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Fisher Exact
	Comments

10. Secondary Outcome

Title	Duration of Neutropenia
Description	Median number of days patients were neutropenic during the study period
Time Frame	11/1/2005 - 10/31/2007

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Caspofungin Arm	Micafungin Arm
Arm/Group Description	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
Measure Participants	149	174
Median (Inter-Quartile Range) [days]	20	17

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Caspofungin Arm, Micafungin Arm
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Fisher Exact
	Comments

Adverse Events

Arm/Group Title	Caspofungin Arm		Micafungin Arm
Arm/Group Description	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
All Cause Mortality
	Caspofungin Arm		Micafungin Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Caspofungin Arm		Micafungin Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/149 (2%)		2/174 (1.1%)
Hepatobiliary disorders
Liver function test elevation	0/149 (0%)	0	1/174 (0.6%)	1
Immune system disorders
Anaphylaxis	1/149 (0.7%)	1	0/174 (0%)	0
Skin and subcutaneous tissue disorders
Rash	2/149 (1.3%)	2	1/174 (0.6%)	1
Other (Not Including Serious) Adverse Events
	Caspofungin Arm		Micafungin Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/149 (10.1%)		18/174 (10.3%)
Hepatobiliary disorders
AST > 5x ULN	14/149 (9.4%)	14	15/174 (8.6%)	15
ALT > 5x ULN	10/149 (6.7%)	10	9/174 (5.2%)	9

Limitations/Caveats

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.

More Information

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.