title: Immediate versus deferred empirical antifungal (IDEA) therapy in high-risk patients with febrile neutropenia: a randomized, double-blind, placebo-controlled, multicenter study.
abstract: Empirical antifungal therapy is widely used in high-risk neutropenic hematology patients with fever persisting for more than 4 days. This clinical trial assessed whether immediate empirical therapy with voriconazole could lower the rates of invasive fungal infections (IFIs) compared with this approach. In a double-blind, placebo-controlled, multicenter study, patients with acute leukemia undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) recipients were randomized to broad-spectrum antibacterial therapy plus voriconazole (immediate) or placebo (deferred) after the onset of neutropenic fever. If fever persisted for 96 h, patients were switched to open-label intravenous voriconazole; oral treatment was permitted after 96 h. The primary endpoint was the rate of proven/probable IFIs between Days 2 and 28 after fever onset in the modified intent-to-treat (mITT) complete-case population. One hundred and forty-seven patients were randomized to immediate (n = 81) or deferred (n = 66) voriconazole. In the mITT population, six patients in the immediate group and nine in the deferred group developed proven/probable IFI between Days 2 and 28 (p = 0.258). The safety profiles were similar in both groups. While immediate empirical therapy with voriconazole appears to be safe in febrile neutropenic high-risk patients, it was not associated with a significant reduction in IFIs compared with therapy deferred for 96 h after fever onset.
authors.affiliation: Klinikum Ernst von Bergmann, Charlottenstrasse 72, 14467 Potsdam, Germany. gmaschmeyer@klinikumevb.de
authors.forename: G
authors.initials: G
authors.lastname: Maschmeyer
authors.forename: W J
authors.initials: WJ
authors.lastname: Heinz
authors.forename: B
authors.initials: B
authors.lastname: Hertenstein
authors.forename: H-A
authors.initials: HA
authors.lastname: Horst
authors.forename: C
authors.initials: C
authors.lastname: Requadt
authors.forename: T
authors.initials: T
authors.lastname: Wagner
authors.forename: O A
authors.initials: OA
authors.lastname: Cornely
authors.forename: J
authors.initials: J
authors.lastname: Löffler
authors.forename: M
authors.initials: M
authors.lastname: Ruhnke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005334:Fever / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007938:Leukemia / Q000097:blood / Q000382:microbiology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy / Q000517:prevention & control*; D009503:Neutropenia / Q000188:drug therapy* / Q000382:microbiology; D010919:Placebos; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D010919:Placebos; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole