An open label non-inferiority randomized control trial comparing nebulized amphotericin B with oral itraconazole in patients with pulmonary aspergilloma.

Background Pulmonary aspergilloma (PA) is a common complication seen in patients with pulmonary tuberculosis sequelae. Antifungal therapy, including oral azoles, is commonly used though only surgical resection offers curative benefit. Local administration of amphotericin B like intracavitary instillation, has been effective in aspergilloma patients though nebulized amphotericin B (nAB) has never been formally assessed. Objective The aim of this prospective, non-inferior, open label, randomized controlled trial is to evaluate the efficacy and safety of nebulized amphotericin B compared to oral itraconazole therapy in the treatment of PA. Patients/methods Diagnosed cases of PA(n=32) were randomized into the control group receiving oral itraconazole (n=17) and intervention group receiving nebulized amphotericin B (n=15) . Response to treatment was assessed both clinically and radiologically at the end 6 months. Results and conclusion The number of patients showing overall improvement at the end of 6 months in the control arm(oral itraconazole) vs intervention arm(nebulized amphotericin B) was 65% (95% CI 38.3-85.8) , and 67%(95% CI 38.4% - 88.2%) respectively in the intention-to-treat and 79% (95% CI 49.2-95.3%), and 65% (95% CI 38.4% - 88.2%) respectively in the per-protocol analysis. While, there was no statistically significant difference between the intervention and control arm in both the analyses, non-inferiority was shown in the per-protocol but not in the intention-to-treat analysis. No major adverse events were noted in either group, however a significant proportion of patients receiving nAB reported minor cough (40%), which however did not lead to discontinuation of therapy in any patients. Nebulized amphotericin B can be an effective therapeutic option for pulmonary aspergilloma patients.