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).
CONCLUSIONS: 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.
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).
CONCLUSIONS: 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.
摘要：
背景：两性霉素B（NAB）雾化治疗肺毛霉菌病（PM）的作用尚不清楚。
方法：在这项开放标签试验中，我们随机分配PM受试者接受静脉注射脂质体两性霉素B(对照组，3-5mg/kg/天）单独或与雾化的两性霉素B脱氧胆酸盐（NAB，每天两次10毫克，每隔一天)。主要结果是：（1）总体反应（\'成功\'[完全或部分反应]或\'失败\'[稳定的疾病，进行性疾病,或死亡]）在6周时；和（2）患有不良事件（AE）的受试者比例。关键的次要结局是90天死亡率。我们进行了改良的意向治疗（mITT）分析，其中我们仅包括接受至少单剂量NAB的受试者。
结果：15名和17名受试者被随机分配到对照组和NAB组；2名受试者在第一次给NAB前死亡。最后,我们纳入了30名受试者(每组15名;平均年龄49.8岁;80%为男性)进行mITT分析.糖尿病（n=27；16/27为COVID-19相关PM）是最常见的诱发因素。对照组和NAB组之间的总体治疗成功率没有显着差异（71.4％vs.53.3%；p=.45）。29名受试者经历了任何AE，但没有人停止治疗。对照组（28.6％）和NAB组（53.3％；p=0.26）之间的90天死亡率没有显着差异。
结论：辅助NAB是安全的，但在6周时没有改善总体反应。不同的给药方案或雾化脂质体两性霉素B可能仍需要评估。需要更多的研究来探索PM的其他治疗方案。
方法：在这项开放标签试验中，我们随机分配PM受试者接受静脉注射脂质体两性霉素B(对照组，3-5mg/kg/天）单独或与雾化的两性霉素B脱氧胆酸盐（NAB，每天两次10毫克，每隔一天)。主要结果是：（1）总体反应（\'成功\'[完全或部分反应]或\'失败\'[稳定的疾病，进行性疾病,或死亡]）在6周时；和（2）患有不良事件（AE）的受试者比例。关键的次要结局是90天死亡率。我们进行了改良的意向治疗（mITT）分析，其中我们仅包括接受至少单剂量NAB的受试者。
结果：15名和17名受试者被随机分配到对照组和NAB组；2名受试者在第一次给NAB前死亡。最后,我们纳入了30名受试者(每组15名;平均年龄49.8岁;80%为男性)进行mITT分析.糖尿病（n=27；16/27为COVID-19相关PM）是最常见的诱发因素。对照组和NAB组之间的总体治疗成功率没有显着差异（71.4％vs.53.3%；p=.45）。29名受试者经历了任何AE，但没有人停止治疗。对照组（28.6％）和NAB组（53.3％；p=0.26）之间的90天死亡率没有显着差异。
结论：辅助NAB是安全的，但在6周时没有改善总体反应。不同的给药方案或雾化脂质体两性霉素B可能仍需要评估。需要更多的研究来探索PM的其他治疗方案。
