Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA
Six Months Versus 12 Months of Oral Itraconazole Therapy for Management of Treatment naïve Subjects With CPA
The treatment options majorly consist of medical management with at least 6-month long
 treatment with antifungal drugs - most significantly the azole groups. Itraconazole is the
 preferred azole for the treatment of CPA. The duration of treatment with oral itraconazole
 remains uncertain. In a previous study the use of oral itraconazole for 6-months a favorable
 overall response was seen in 76% of the subjects. Moreover, about 30%-50% of the subjects
 have disease relapse that requires prolonged therapy. It is likely that a longer duration of
 itraconazole would have a higher response rate and thus, lower risk of relapse after
 discontinuation of therapy. In this randomized controlled trial, we compare the clinical
 outcomes of six months versus twelve months of itraconazole therapy in treatment naïve
 subjects with chronic pulmonary aspergillosis
Aspergillus is a saprophytic fungus which is present normally in our surroundings and causes
 a large number of pulmonary diseases spreading through inhalational route. The spectrum of
 disease caused by aspergillus spp. is wide with the manifestations of the disease being
 governed primarily by the status of the underlying host immunity, which then determines the
 nature of the host-aspergillus interaction. Patients with an intact immunity have a more
 stable and indolent form of disease like aspergilloma whereas with a worsening immune status,
 the risk of invasive disease increases. Chronic pulmonary aspergillosis (CPA) and allergic
 bronchopulmonary aspergillosis (ABPA) are two of the commonest pulmonary manifestations seen
 in non-immunocompromised patients whereas invasive pulmonary aspergillosis being more common
 in the immunocompromised patients.

 Estimates suggest that CPA affects around 3 million people across the globe, which may still
 be an under estimated number as the disease co exists with other pulmonary co-morbidities
 which make accurate diagnosis a pitfall. In India the annual incidence of CPA was estimated
 in 2011 and varied between 27,000-0.17 million cases, with different estimates. Based on the
 mortality rate for CPA which was estimated to be 15% annually, the 5-year prevalence of CPA
 was placed at 290,147 cases with 5-year prevalence rate being 24 per 100,000 in the same
 year. The disease confers significant morbidity and mortality, making it a significant burden
 for the society as well as the healthcare. Apart from the respiratory symptoms, CPA causes
 significant constitutional symptoms as well which adds to the misery of the patient. The
 diagnosis of CPA is based on presence of chronic symptoms, consistent radiology and
 demonstration of Aspergillus by direct (culture) or indirect (serological) methods. Even
 though CPA is more of a disease spectrum but overall it is characterized by slowly
 progressive lung cavitation which may or may not show presence of mycetoma /fungal ball in
 patients with pre-existing structural lung diseases, even though other patterns have also
 been identified.

 The treatment options majorly consist of medical management with at least 6-month long
 treatment with antifungal drugs - most significantly the azole groups. Itraconazole is the
 preferred azole for the treatment of CPA. The duration of treatment with oral itraconazole
 remains uncertain. In a previous study the use of oral itraconazole for 6-months a favorable
 overall response was seen in 76% of the subjects. Moreover, about 30%-50% of the subjects
 have disease relapse that requires prolonged therapy. It is likely that a longer duration of
 itraconazole would have a higher response rate and thus, lower risk of relapse after
 discontinuation of therapy. In this randomized controlled trial, we compare the clinical
 outcomes of six months versus twelve months of itraconazole therapy in treatment naïve
 subjects with chronic pulmonary aspergillosis.
Inclusion Criteria: includes presence of all the following:

 -  one or more clinical symptoms (persistent cough, recurrent hemoptysis, weight loss,
 malaise, fever and dyspnea) for ≥3 months

 -  slowly progressive or persistent radiological findings (one or more cavities and
 surrounding fibrosis, infiltrates, consolidation, with or without fungal ball or
 progressive pleural thickening) on computed tomography (CT) of the thorax

 -  immunological (A.fumigatus-specific IgG >27 mgA/L or positive Aspergillus precipitins)
 or microbiological evidence of Aspergillus infection (growth of Aspergillus in
 respiratory secretions or serum galactomannan index >0.5 or BALF galactomannan index
 >1) and,

 -  exclusion of other pulmonary disorders with similar presentation.

 Exclusion Criteria:

 -  failure to provide informed consent

 -  patients on immunosuppressive drugs, intake of prednisolone (or equivalent) >10 mg for
 at least 3 weeks or a diagnosis of human immunodeficiency virus syndrome

 -  intake antifungal azoles for >3 weeks in the preceding six months

 -  subjects with active pulmonary infection due to mycobacterium tuberculosis or
 mycobacteria other than tuberculosis (MOTT)

 -  subjects with others forms of pulmonary aspergillosis (allergic bronchopulmonary
 aspergillosis, chronic necrotizing aspergillosis and angio-invasive aspergillosis)

 -  pregnancy