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

Publication Type
Journal Article
Year of Publication
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 T; Stadtmauer, Edward A; BolaƱos-Meade, Javier; Brown, Janice; Dipersio, John F; Boeckh, Michael; Marr, Kieren A; Blood and Marrow Transplant Clinical Trials Network
Date Published
2010 Dec 09
Adolescent; Adult; Aged; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Disease-Free Survival; Double-Blind Method; Drug Monitoring; Fluconazole; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Mannans; Middle Aged; Mycoses; Myeloablative Agonists; Survival Rate; Transplantation, Homologous; Young Adult

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.