Aerosolized liposomal amphotericin B for the prevention of invasive pulmonary aspergillosis during prolonged neutropenia: A randomized, placebo-controlled trial

Background. Invasive pulmonary aspergillosis ( IPA) is a significant problem in patients with chemotherapy-induced prolonged neutropenia. Because pulmonary deposition of conidia is the first step in developing IPA, we hypothesized that inhalation of liposomal amphotericin B would prevent IPA. Methods. We performed a randomized, placebo- controlled trial of patients with hematologic disease with expected neutropenia for >= 10 days. Patients were randomized to receive liposomal amphotericin B or placebo inhalation twice a week, using an adaptive aerosol delivery system, until neutrophil counts increased to >300 cells/ mm(3). In subsequent neutropenic episodes, the assigned treatment was restarted. The primary end point was the occurrence of IPA according to European Organization for Research and the Treatment of Cancer- Mycoses Study Group definitions. Kaplan- Meier curves were compared with log- rank tests for intent- to- treat and on- treatment populations. Results. A total of 271 patients were studied during 407 neutropenic episodes. According to the intent- to-treat analysis, 18 of 132 patients in the placebo group developed IPA versus 6 of 139 patients in the liposomal amphotericin B group ( odds ratio, 0.26; 95% confidence interval, 0.09 - 0.72;P=.005). According to the on- 005 treatment analysis, 13 of 97 patients receiving placebo versus 2 of 91 receiving liposomal amphotericin B developed IPA ( odds ratio, 0.14; 95% confidence interval, 0.02 - 0.66;). Some adverse effects, but none serious, in Pp. 007 the liposomal amphotericin B group were reported, most frequently coughing ( 16 patients vs. 1 patient; P=.002) Conclusion. In high- risk patients, prophylactic inhalation of liposomal amphotericin B significantly reduced the incidence of IPA.