Abstract
Background In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. Methods We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after a 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal-amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time-to-first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. Results Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) of 65 patients in nebulised liposomal-amphotericin-B group and 38 (51.3%) of 74 in placebo group (absolute difference −0.6%, 95% CI −16.8% to +15.6%, odds ratio 0.98, 95% CI 0.50 to 1.90; p=0.95). The median time-to-first severe clinical exacerbation was longer in liposomal-amphotericin-B group, 337 days (IQR, 168 to 476) versus 177 (64 to 288). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in nebulised liposomal-amphotericin-B group. Conclusions In ABPA, maintenance therapy using nebulised liposomal-amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.