A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin b for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia

Johan A. Maertens, Luis Madero, Anne F. Reilly, Thomas Lehrnbecher, Andreas H. Groll, Hasan S. Jafri, Michael Green, Joseph J. Nania, Michael R. Bourque, Beth Ann Wise, Kim M. Strohmaier, Arlene F. Taylor, Nicholas A. Kartsonis, Joseph W. Chow, Carola A.S. Arndt, Ben E. Depauw, Thomas J. Walsh

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

BACKGROUND: Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients. METHODS: Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or l-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee. RESULTS: Eighty-two patients received study therapy (caspofungin 56, l-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; l-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95% confidence interval] were similar between the caspofungin and l-AmB groups (clinical 48.2% [34.7-62.0] versus 46.2% [26.6-66.6]; laboratory 10.7% [4.0-21.9] versus 19.2% [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8%) of caspofungin-treated patients and 3 (11.5%) of l-AmB-treated patients. Overall success rates [95% CI] were 46.4% [33.4-59.5] for caspofungin and 32.0% [13.7-50.3] for l-AmB. CONCLUSIONS: Caspofungin and l-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.

Original languageEnglish (US)
Pages (from-to)415-420
Number of pages6
JournalPediatric Infectious Disease Journal
Volume29
Issue number5
DOIs
StatePublished - May 2010

Fingerprint

caspofungin
Amphotericin B
Neutropenia
Double-Blind Method
Multicenter Studies
Fever
Pediatrics
Drug-Related Side Effects and Adverse Reactions
Safety
Therapeutics
Echinocandins
Standard of Care

Keywords

  • Caspofungin
  • Empiric antifungal therapy
  • Fever and neutropenia
  • Liposomal amphotericin B
  • Pediatric patients

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Infectious Diseases
  • Microbiology (medical)

Cite this

A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin b for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia. / Maertens, Johan A.; Madero, Luis; Reilly, Anne F.; Lehrnbecher, Thomas; Groll, Andreas H.; Jafri, Hasan S.; Green, Michael; Nania, Joseph J.; Bourque, Michael R.; Wise, Beth Ann; Strohmaier, Kim M.; Taylor, Arlene F.; Kartsonis, Nicholas A.; Chow, Joseph W.; Arndt, Carola A.S.; Depauw, Ben E.; Walsh, Thomas J.

In: Pediatric Infectious Disease Journal, Vol. 29, No. 5, 05.2010, p. 415-420.

Research output: Contribution to journalArticle

Maertens, JA, Madero, L, Reilly, AF, Lehrnbecher, T, Groll, AH, Jafri, HS, Green, M, Nania, JJ, Bourque, MR, Wise, BA, Strohmaier, KM, Taylor, AF, Kartsonis, NA, Chow, JW, Arndt, CAS, Depauw, BE & Walsh, TJ 2010, 'A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin b for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia', Pediatric Infectious Disease Journal, vol. 29, no. 5, pp. 415-420. https://doi.org/10.1097/INF.0b013e3181da2171
Maertens, Johan A. ; Madero, Luis ; Reilly, Anne F. ; Lehrnbecher, Thomas ; Groll, Andreas H. ; Jafri, Hasan S. ; Green, Michael ; Nania, Joseph J. ; Bourque, Michael R. ; Wise, Beth Ann ; Strohmaier, Kim M. ; Taylor, Arlene F. ; Kartsonis, Nicholas A. ; Chow, Joseph W. ; Arndt, Carola A.S. ; Depauw, Ben E. ; Walsh, Thomas J. / A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin b for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia. In: Pediatric Infectious Disease Journal. 2010 ; Vol. 29, No. 5. pp. 415-420.
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abstract = "BACKGROUND: Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients. METHODS: Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or l-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee. RESULTS: Eighty-two patients received study therapy (caspofungin 56, l-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; l-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95{\%} confidence interval] were similar between the caspofungin and l-AmB groups (clinical 48.2{\%} [34.7-62.0] versus 46.2{\%} [26.6-66.6]; laboratory 10.7{\%} [4.0-21.9] versus 19.2{\%} [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8{\%}) of caspofungin-treated patients and 3 (11.5{\%}) of l-AmB-treated patients. Overall success rates [95{\%} CI] were 46.4{\%} [33.4-59.5] for caspofungin and 32.0{\%} [13.7-50.3] for l-AmB. CONCLUSIONS: Caspofungin and l-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.",
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T1 - A randomized, double-blind, multicenter study of caspofungin versus liposomal amphotericin b for empiric antifungal therapy in pediatric patients with persistent fever and neutropenia

AU - Maertens, Johan A.

AU - Madero, Luis

AU - Reilly, Anne F.

AU - Lehrnbecher, Thomas

AU - Groll, Andreas H.

AU - Jafri, Hasan S.

AU - Green, Michael

AU - Nania, Joseph J.

AU - Bourque, Michael R.

AU - Wise, Beth Ann

AU - Strohmaier, Kim M.

AU - Taylor, Arlene F.

AU - Kartsonis, Nicholas A.

AU - Chow, Joseph W.

AU - Arndt, Carola A.S.

AU - Depauw, Ben E.

AU - Walsh, Thomas J.

PY - 2010/5

Y1 - 2010/5

N2 - BACKGROUND: Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients. METHODS: Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or l-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee. RESULTS: Eighty-two patients received study therapy (caspofungin 56, l-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; l-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95% confidence interval] were similar between the caspofungin and l-AmB groups (clinical 48.2% [34.7-62.0] versus 46.2% [26.6-66.6]; laboratory 10.7% [4.0-21.9] versus 19.2% [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8%) of caspofungin-treated patients and 3 (11.5%) of l-AmB-treated patients. Overall success rates [95% CI] were 46.4% [33.4-59.5] for caspofungin and 32.0% [13.7-50.3] for l-AmB. CONCLUSIONS: Caspofungin and l-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.

AB - BACKGROUND: Persistently febrile neutropenic children at risk for invasive fungal infections receive empiric antifungal therapy as a standard of care. However, little is known about the role of echinocandins and liposomal amphotericin B (L-AmB) for empiric antifungal therapy in pediatric patients. METHODS: Patients between the ages of 2 to 17 years with persistent fever and neutropenia were randomly assigned to receive caspofungin (70 mg/m loading dose on day 1, then 50 mg/m daily [maximum 70 mg/d]) or l-AmB (3 mg/kg daily) in a 2:1 ratio. Evaluation of safety was the primary objective of the study. Efficacy was also evaluated, with a successful outcome defined as fulfilling all components of a prespecified 5-part composite endpoint. Suspected invasive fungal infections were evaluated by an independent, treatment-blinded adjudication committee. RESULTS: Eighty-two patients received study therapy (caspofungin 56, l-AmB 26), and 81 were evaluated for efficacy (caspofungin 56; l-AmB 25). Outcomes for safety and efficacy endpoints were similar for both study arms. Adverse drug-related event rates [95% confidence interval] were similar between the caspofungin and l-AmB groups (clinical 48.2% [34.7-62.0] versus 46.2% [26.6-66.6]; laboratory 10.7% [4.0-21.9] versus 19.2% [6.6-39.4]). Serious drug-related adverse events occurred in 1 (1.8%) of caspofungin-treated patients and 3 (11.5%) of l-AmB-treated patients. Overall success rates [95% CI] were 46.4% [33.4-59.5] for caspofungin and 32.0% [13.7-50.3] for l-AmB. CONCLUSIONS: Caspofungin and l-AmB were comparable in tolerability, safety, and efficacy as empiric antifungal therapy for persistently febrile neutropenic pediatric patients.

KW - Caspofungin

KW - Empiric antifungal therapy

KW - Fever and neutropenia

KW - Liposomal amphotericin B

KW - Pediatric patients

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