Aerosolized Liposomal Amphotericin B for the Prevention of Invasive Pulmonary Aspergillosis during Prolonged Neutropenia: A Randomized, Placebo-Controlled Trial

• Published in: Clinical infectious diseases 2008-05, Vol.46 (9), p.1401-1408
• Main Authors: Rijnders, Bart J., Cornelissen, Jan J., Slobbe, Lennert, Becker, Martin J., Doorduijn, Jeanette K., Hop, Wim C. J., Ruijgrok, Elisabeth J., Lüwenberg, Bob, Vulto, Arnold, Lugtenburg, Pieternella J., de Marie, Siem
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adolescent; Adult; Aerosols; Aged; Amphotericin B - administration & dosage; Amphotericin B - therapeutic use; Antifungal Agents - administration & dosage; Antifungal Agents - therapeutic use; Articles and Commentaries; Aspergillosis - etiology; Aspergillosis - prevention & control; Aspergillus; Chemotherapy; Clinical trials; Disease prevention; Female; Humans; Inhalation; Invasive pulmonary aspergillosis; Kaplan-Meier Estimate; Lung Diseases, Fungal - etiology; Lung Diseases, Fungal - prevention & control; Male; Middle Aged; Mortality; Neutropenia; Neutropenia - complications; Neutrophils; Placebos; Respiratory diseases; Respiratory therapy; Studies; Treatment Outcome
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/586739

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/mm3. 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-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; P=.007). Some adverse effects, but none serious, in 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.