NCT05444946

Oral Itraconazole Versus Combination of Systemic Glucorticoids and Oral Itraconazole in CPA-ABPA Overlap Syndrome

A Randomized Controlled Trial to Compare Oral Itraconazole Versus Combination of Systemic Glucorticoids and Oral Itraconazole in Chronic Pulmonary and Allergic Bronchopulmonary Aspergillosis Overlap Syndrome

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 104 (estimated)
• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh · Academic / Other
• Sex: All
• Age: 15 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

While ABPA and CPA represent two distinct manifestations of Aspergillus-related lung disease, there is an overlap of investigations that are currently used for the diagnosis of these entities. In a previous study, the authors have demonstrated that 22% of subjects with CPA fulfilled the obligatory criteria for ABPA. While the preferable therapy in patients with ABPA is systemic glucocorticoids, the primary therapy in CPA is oral triazoles. However, a different management protocol in the "overlap group" with low doses of glucocorticoids and triazoles, needs to be systematically explored. In this study the investigators intend to compare the clinical outcomes in subjects with ABPA-CPA overlap treated either with oral azoles or a combination of systemic glucocorticoids and oral azoles.

Detailed description

Aspergillus causes a variety of pulmonary disorders depending on the host immunity. In immunocompetent hosts, it can cause allergic diseases, the prototype being allergic bronchopulmonary aspergillosis (ABPA). In immunosuppressed host, it causes life-threatening invasive disease. Chronic pulmonary aspergillosis (CPA) represents chronic Aspergillus infection of the pulmonary parenchyma in subjects with normal or slightly suppressed immunity, and generally an underlying structural lung disease (previously treated pulmonary tuberculosis, chronic obstructive pulmonary disease, sarcoidosis, diffuse parenchymal lung disease and others). The diagnosis of CPA is based on the presence of clinical symptoms (low-grade fever, weight loss, malaise, chronic cough, recurrent hemoptysis and others), radiological features (combination of one or more cavities and presence of fungal ball or fibrosis, pericavitary infiltrates, consolidation, nodules and pleural thickening) and the demonstration of either direct (growth of Aspergillus on sputum or bronchoalveolar lavage fluid \[BALF\] culture) or indirect (elevated serum or BALF galactomannan index or A.fumigatus-specific IgG or precipitin in serum) evidence of Aspergillus infection. Primarily seen in patients with asthma and cystic fibrosis, the diagnosis of ABPA is currently made on the combination of clinical (low grade fever, hemoptysis and others), radiological (bronchiectasis, mucus impaction, centrilobular nodules and others) and immunological (A.fumigatus-specific IgE and IgG, total IgE, and elevated eosinophils) findings. While ABPA and CPA represent two distinct manifestations of Aspergillus-related lung disease, there is an overlap of investigations that are currently used for the diagnosis of these entities. For example, A.fumigatus-specific IgG and Aspergillus precipitins are used both in diagnosing ABPA and CPA.(10) The culture of respiratory tract secretions can demonstrate the growth of Aspergillus in both these disorders. Also, ABPA is a predisposing condition for developing CPA and it is likely that both ABPA and CPA may coexist. In a previous study, the authors have demonstrated that 22% of subjects with CPA fulfilled the obligatory criteria for ABPA. While CPA is primarily due to dysfunction of Th-1 immunity, ABPA represents an inflammatory response due to Th-2 hyper response. Thus, it is possible that subjects with ABPA-CPA overlap could have components of both heightened inflammatory response and local immune dysfunction thereby perpetuating structural lung damage. While the preferable therapy in patients with ABPA is systemic glucocorticoids, the primary therapy in CPA is oral triazoles. However, a different management protocol in the "overlap group" with low doses of glucocorticoids and triazoles, needs to be systematically explored. In this study the investigators intend to compare the clinical outcomes in subjects with ABPA-CPA overlap treated either with oral azoles or a combination of systemic glucocorticoids and oral azoles.

Conditions

• Chronic Pulmonary Aspergillosis
• Allergic Bronchopulmonary Aspergillosis

Interventions

Type	Name	Description
DRUG	Prednisone tablet and Itraconazole	Oral prednisolone 0.5 mg/Kg body weight tapered over 4 months and oral itraconazole (400 mg/day). The dose of itraconazole will be adjusted according to therapeutic drug monitoring to achieve a serum trough level of 0.5 microgram/mL. traconazole will be given for 12 months
DRUG	Oral itraconazole	Oral itraconazole (400 mg/day). The dose of itraconazole will be adjusted according to therapeutic drug monitoring to achieve a serum trough level of 0.5 microgram/mL. Itraconazole will be given for 12 months

Timeline

• Start date: 2022-06-15
• Primary completion: 2027-01-31
• Completion: 2027-02-01
• First posted: 2022-07-06
• Last updated: 2026-04-07

Locations

2 sites across 1 country: India