Treatment of pulmonary mucormycosis with adjunctive nebulized amphotericin B (MUCONAB trial): Results of an open‐label randomized controlled trial

Abstract Background The role of nebulized amphotericin B (NAB) in managing pulmonary mucormycosis (PM) is unknown. Methods In this open‐label trial, we randomized PM subjects to receive either intravenous liposomal amphotericin B (control arm, 3–5 mg/kg/day) alone or along with nebulized amphotericin B deoxycholate (NAB, 10 mg twice a day, every alternate day). The primary outcomes were: (1) overall response (‘success’ [complete or partial response] or ‘failure’ [stable disease, progressive disease, or death]) at 6 weeks; and (2) the proportion of subjects with adverse events (AE). The key secondary outcome was 90‐day mortality. We performed a modified intention‐to‐treat (mITT) analysis where we included only subjects receiving at least a single dose of NAB. Results Fifteen and 17 subjects were randomized to the control and NAB arms; two died before the first dose of NAB. Finally, we included 30 subjects (15 in each arm; mean age 49.8 years; 80% men) for the mITT analysis. Diabetes mellitus ( n = 27; 16/27 were COVID‐19‐associated PM) was the most common predisposing factor. The overall treatment success was not significantly different between the control and the NAB arms (71.4% vs. 53.3%; p = .45). Twenty‐nine subjects experienced any AE, but none discontinued treatment. The 90‐day mortality was not significantly different between the control (28.6%) and NAB arm (53.3%; p = .26). Conclusion Adjunctive NAB was safe but did not improve overall response at 6 weeks. A different dosing schedule or nebulized liposomal amphotericin B may still need evaluation. More research is needed to explore other treatment options for PM.