A Study of Itraconazole and Posaconazole for Chronic Pulmonary Aspergillosis

A prospective, randomized, open-label comparative study evaluating oral itraconazole and oral posaconazole in treatment-naïve patients with CPA, with treatment for 12 months is proposed. The study will compare clinical effectiveness and safety of the study drugs. The findings will generate evidence to guide individualized antifungal therapy, inform antifungal stewardship strategies, and strengthen resistance surveillance frameworks for CPA. As the first randomized evaluation of posaconazole in CPA, the study has the potential to directly influence clinical practice and international treatment recommendations for this neglected fungal disease

Inclusion Criteria: * One or more clinical symptoms (persistent cough, recurrent haemoptysis, weight loss, malaise, fever, dyspnoea) for ≥3 months * Slowly progressive or persistent radiological findings on CT thorax including one or more cavities with or without a fungal ball, fibrosis, pericavitary infiltrates, consolidation, nodules, or pleural thickening * Serum A. fumigatus-IgG ≥27 milligrams of antibody/litre (mgA/L), or growth of Aspergillus in respiratory secretions (twice in sputum or once in bronchoalveolar lavage fluid \[BALF\]) or serum galactomannan index (GMI) ≥1.7 or BALF GMI ≥2.6. * Exclusion of other pulmonary disorders with similar presentation (active pulmonary TB, malignancy, other infections) Exclusion Criteria: * Failure or refusal to provide written informed consent * Patients on immunosuppressive drugs, receiving prednisolone (or equivalent) ≥10 mg/day for ≥3 weeks, or known HIV infection * Intake of antifungal triazoles for ≥3 weeks in the preceding 3 months (prior azole therapy) * Active pulmonary infection due to Mycobacterium tuberculosis or non-tuberculous mycobacteria * Other forms of pulmonary aspergillosis (subacute or acute invasive aspergillosis) * Pregnancy or lactation * Significant hepatic dysfunction (ALT/AST ≥3× upper limit of normal at baseline) * Known hypersensitivity to azole antifungals