Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis

Raoul Herbrecht, David W. Denning, Thomas F. Patterson, John E. Bennett, Reginald E. Greene, Jörg W. Oestmann, Winfried V. Kern, Kieren A. Marr, Patricia Ribaud, Olivier Lortholary, Richard Sylvester, Robert H. Rubin, John R. Wingard, Paul Stark, Christine Durand, Denis Caillot, Eckhard Thiel, Pranatharthi H. Chandrasekar, Michael R. Hodges, Haran T. SchlammPeter F. Troke, Ben De Pauw

    Research output: Contribution to journalArticlepeer-review


    Background: Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. Methods: In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. Results: A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). Conclusions: In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B. Copyright © 2002 Massachusetts Medical Society.
    Original languageEnglish
    Pages (from-to)408-415
    Number of pages7
    JournalNew England Journal Of Medicine
    Issue number6
    Publication statusPublished - 8 Aug 2002


    • Adolescent
    • Adult
    • Aged
    • adverse effects: Amphotericin B
    • adverse effects: Antifungal Agents
    • drug therapy: Aspergillosis
    • Comparative Study
    • Female
    • complications: Hematologic Diseases
    • Human
    • Infusions, Intravenous
    • Male
    • Middle Age
    • adverse effects: Pyrimidines
    • Support, Non-U.S. Gov't
    • Survival Rate
    • adverse effects: Triazoles


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