Randomized, double-blind trial of fluconazole versus voriconazole for prevention of invasive fungal infection after allogeneic hematopoietic cell transplantation Journal Article
| Authors: | Wingard, J. R.; Carter, S. L.; Walsh, T. J.; Kurtzberg, J.; Small, T. N.; Baden, L. R.; Gersten, I. D.; Mendizabal, A. M.; Leather, H. L.; Confer, D. L.; Maziarz, R. T.; Stadtmauer, E. A.; Bolaños-Meade, J.; Brown, J.; DiPersio, J. F.; Boeckh, M.; Marr, K. A. |
| Article 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 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. © 2010 by The American Society of Hematology. |
| Keywords: | adolescent; adult; child; controlled study; preschool child; school child; aged; child, preschool; disease-free survival; middle aged; survival rate; transplantation, homologous; young adult; major clinical study; overall survival; prednisone; clinical trial; placebo; drug dose comparison; drug efficacy; drug safety; drug withdrawal; treatment duration; disease free survival; controlled clinical trial; randomized controlled trial; hematopoietic stem cell transplantation; high risk patient; myeloablative conditioning; hematologic neoplasms; multicenter study; allogeneic hematopoietic stem cell transplantation; drug monitoring; infection prevention; double blind procedure; double-blind method; visual disorder; fluconazole; treatment withdrawal; voriconazole; antifungal agents; aspergillus; aspergillosis; graft recipient; galactomannan; mannans; systemic mycosis; mycoses; myeloablative agonists |
| Journal Title: | Blood |
| Volume: | 116 |
| Issue: | 24 |
| ISSN: | 0006-4971 |
| Publisher: | American Society of Hematology |
| Date Published: | 2010-12-09 |
| Start Page: | 5111 |
| End Page: | 5118 |
| Language: | English |
| DOI: | 10.1182/blood-2010-02-268151 |
| PUBMED: | 20826719 |
| PROVIDER: | scopus |
| PMCID: | PMC3012532 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 20 April 2011" - "CODEN: BLOOA" - "Source: Scopus" |
