Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation

John R. Wingard, Shelly L. Carter, Thomas J. Walsh, Joanne Kurtzberg, Trudy N. Small, Lindsey R. Baden, Iris D. Gersten, Adam M. Mendizabal, Helen L. Leather, Dennis L. Confer, Richard Maziarz, Edward A. Stadtmauer, Javier Bolaños-Meade, Janice Brown, John F. DiPersio, Michael Boeckh, Kieren A. Marr

Research output: Contribution to journalArticle

305 Citations (Scopus)

Abstract

Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P =.09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and over-all survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.

Original languageEnglish (US)
Pages (from-to)5111-5118
Number of pages8
JournalBlood
Volume116
Issue number24
DOIs
StatePublished - Dec 9 2010

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Transplants
Fluconazole
Cell Transplantation
Survival
Aspergillus
Screening
Recurrence
Voriconazole
Invasive Fungal Infections
Monitoring
Incidence
Therapeutics
Infection
Serum
Pharmaceutical Preparations
galactomannan

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. / Wingard, John R.; Carter, Shelly L.; Walsh, Thomas J.; Kurtzberg, Joanne; Small, Trudy N.; Baden, Lindsey R.; Gersten, Iris D.; Mendizabal, Adam M.; Leather, Helen L.; Confer, Dennis L.; Maziarz, Richard; Stadtmauer, Edward A.; Bolaños-Meade, Javier; Brown, Janice; DiPersio, John F.; Boeckh, Michael; Marr, Kieren A.

In: Blood, Vol. 116, No. 24, 09.12.2010, p. 5111-5118.

Research output: Contribution to journalArticle

Wingard, JR, Carter, SL, Walsh, TJ, Kurtzberg, J, Small, TN, Baden, LR, Gersten, ID, Mendizabal, AM, Leather, HL, Confer, DL, Maziarz, R, Stadtmauer, EA, Bolaños-Meade, J, Brown, J, DiPersio, JF, Boeckh, M & Marr, KA 2010, 'Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation', Blood, vol. 116, no. 24, pp. 5111-5118. https://doi.org/10.1182/blood-2010-02-268151
Wingard, John R. ; Carter, Shelly L. ; Walsh, Thomas J. ; Kurtzberg, Joanne ; Small, Trudy N. ; Baden, Lindsey R. ; Gersten, Iris D. ; Mendizabal, Adam M. ; Leather, Helen L. ; Confer, Dennis L. ; Maziarz, Richard ; Stadtmauer, Edward A. ; Bolaños-Meade, Javier ; Brown, Janice ; DiPersio, John F. ; Boeckh, Michael ; Marr, Kieren A. / Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation. In: Blood. 2010 ; Vol. 116, No. 24. pp. 5111-5118.
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abstract = "Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3{\%} vs 11.2{\%}; P = .12), Aspergillus infections (9 vs 17; P =.09), and less frequent empiric antifungal therapy (24.1{\%} vs 30.2{\%}, P = .11) with voriconazole, FFS rates (75{\%} vs 78{\%}; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and over-all survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.",
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T1 - Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation

AU - Wingard, John R.

AU - Carter, Shelly L.

AU - Walsh, Thomas J.

AU - Kurtzberg, Joanne

AU - Small, Trudy N.

AU - Baden, Lindsey R.

AU - Gersten, Iris D.

AU - Mendizabal, Adam M.

AU - Leather, Helen L.

AU - Confer, Dennis L.

AU - Maziarz, Richard

AU - Stadtmauer, Edward A.

AU - Bolaños-Meade, Javier

AU - Brown, Janice

AU - DiPersio, John F.

AU - Boeckh, Michael

AU - Marr, Kieren A.

PY - 2010/12/9

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N2 - Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P =.09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and over-all survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.

AB - Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice weekly for 60 days, then at least weekly until day 100. Positive galactomannan or suggestive signs triggered mandatory evaluation for IFI. The primary endpoint was freedom from IFI or death (fungal-free survival; FFS) at 180 days. Despite trends to fewer IFIs (7.3% vs 11.2%; P = .12), Aspergillus infections (9 vs 17; P =.09), and less frequent empiric antifungal therapy (24.1% vs 30.2%, P = .11) with voriconazole, FFS rates (75% vs 78%; P = .49) at 180 days were similar with fluconazole and voriconazole, respectively. Relapse-free and over-all survival and the incidence of severe adverse events were also similar. This study demonstrates that in the context of intensive monitoring and structured empiric antifungal therapy, 6-month FFS and overall survival did not differ in allogeneic HCT recipients given prophylactic fluconazole or voriconazole. This trial was registered at www.clinicaltrials.gov as NCT00075803.

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