title: Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation.
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 overall 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.
authors.affiliation: University of Florida, Gainesville, FL, USA. wingajr@medicine.ufl.edu
authors.forename: John R
authors.initials: JR
authors.lastname: Wingard
authors.forename: Shelly L
authors.initials: SL
authors.lastname: Carter
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Walsh
authors.forename: Joanne
authors.initials: J
authors.lastname: Kurtzberg
authors.forename: Trudy N
authors.initials: TN
authors.lastname: Small
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Iris D
authors.initials: ID
authors.lastname: Gersten
authors.forename: Adam M
authors.initials: AM
authors.lastname: Mendizabal
authors.forename: Helen L
authors.initials: HL
authors.lastname: Leather
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Confer
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
authors.forename: Edward A
authors.initials: EA
authors.lastname: Stadtmauer
authors.forename: Javier
authors.initials: J
authors.lastname: Bolaños-Meade
authors.forename: Janice
authors.initials: J
authors.lastname: Brown
authors.forename: John F
authors.initials: JF
authors.lastname: Dipersio
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
authors.forename: Kieren A
authors.initials: KA
authors.lastname: Marr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents; D001228:Aspergillosis / Q000188:drug therapy / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004311:Double-Blind Method; D016903:Drug Monitoring; D015725:Fluconazole / Q000008:administration & dosage* / Q000009:adverse effects; D005690:Galactose / Q000031:analogs & derivatives; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D008351:Mannans / Q000097:blood; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy / Q000517:prevention & control*; D019653:Myeloablative Agonists / Q000627:therapeutic use; D015996:Survival Rate; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D008351:Mannans; D019653:Myeloablative Agonists; C012990:galactomannan; D015725:Fluconazole; D005690:Galactose
references.citation: J Antimicrob Chemother. 2004 Jan;53(1):113-4
references.pmid: 14657088
references.citation: Haematologica. 2010 Oct;95(10):1762-8
references.pmid: 20634495
references.citation: Clin Infect Dis. 2008 Jul 1;47(1):e7-e10
references.pmid: 18491963
references.citation: Clin Infect Dis. 2004 Oct 15;39(8):1241-4
references.pmid: 15486850
references.citation: N Engl J Med. 2007 Jan 25;356(4):335-47
references.pmid: 17251530
references.citation: Clin Infect Dis. 2008 Feb 1;46(3):327-60
references.pmid: 18177225
references.citation: Clin Infect Dis. 2008 May 15;46(10):1626-7; author reply 1627-8
references.pmid: 18419501
references.citation: J Infect Dis. 2005 Apr 15;191(8):1350-60
references.pmid: 15776383
references.citation: J Antimicrob Chemother. 2006 Jun;57(6):1248-50
references.pmid: 16556632
references.citation: Biol Blood Marrow Transplant. 2006 May;12(5):552-9
references.pmid: 16635790
references.citation: Clin Infect Dis. 2007 Feb 1;44(3):373-9
references.pmid: 17205443
references.citation: N Engl J Med. 1992 Mar 26;326(13):845-51
references.pmid: 1542320
references.citation: Clin Infect Dis. 2006 May 15;42(10):1417-27
references.pmid: 16619154
references.citation: Blood. 2004 Feb 15;103(4):1527-33
references.pmid: 14525770
references.citation: N Engl J Med. 2007 Jan 25;356(4):348-59
references.pmid: 17251531
references.citation: Clin Infect Dis. 2004 Oct 15;39 Suppl 4:S176-80
references.pmid: 15546114
references.citation: Blood. 2004 Feb 15;103(4):1557-9
references.pmid: 14504090
references.citation: Clin Infect Dis. 2004 Aug 15;39(4):584-7
references.pmid: 15356827
references.citation: Stat Med. 1999 Mar 30;18(6):695-706
references.pmid: 10204198
references.citation: Clin Infect Dis. 2008 Nov 1;47(9):1176-84
references.pmid: 18808352
references.citation: Cancer. 2007 Apr 15;109(8):1532-5
references.pmid: 17351937
references.citation: Ann Intern Med. 2003 May 6;138(9):705-13
references.pmid: 12729424
references.citation: Clin Infect Dis. 2002 Jan 1;34(1):7-14
references.pmid: 11731939
references.citation: J Infect Dis. 1995 Jun;171(6):1545-52
references.pmid: 7769290
references.citation: N Engl J Med. 2007 Jan 25;356(4):409-11
references.pmid: 17251538
references.citation: Med Mycol. 2005 May;43 Suppl 1:S49-58
references.pmid: 16110792
references.citation: N Engl J Med. 2004 Feb 26;350(9):950-2
references.pmid: 14985500
references.citation: Blood. 2001 Mar 15;97(6):1604-10
references.pmid: 11238098
references.citation: Clin Infect Dis. 2007 Feb 15;44(4):531-40
references.pmid: 17243056
references.citation: Clin Infect Dis. 2010 Apr 15;50(8):1091-100
references.pmid: 20218877