Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis
Condition: Allergic Bronchopulmonary Aspergillosis
MeSH terms: Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      The purpose of this study is to evaluate the efficacy and safety of itraconazole monotherapy
      in patients with ABPA.
    

Detailed description: 
      Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by a complex
      hypersensitivity response to antigens released by the fungus Aspergillus fumigatus. The
      clinical entity was first described by Hinson et al in 1952, and the clinical and immunologic
      significance of Aspergillus fumigatus in the sputum were reported by Pepys and coworkers in
      1959. The prevalence of ABPA in bronchial asthma is fairly high and a recent meta-analysis
      suggested the prevalence of ABPA in asthma clinics to be as high as 13 percent. Diagnostic
      criteria for ABPA have been laid and generally include the following eight major criteria:
      (a) history of asthma; (b) transient or fixed pulmonary infiltrates; (c) immediate cutaneous
      hyperreactivity to A fumigatus antigen; (d) absolute eosinophil count > 1000/µL; (e) serum
      precipitins against A fumigatus; (f) total IgE levels > 1000 IU/mL; (g) central
      bronchiectasis on high-resolution computed tomography (HRCT); and, (h) raised A fumigatus
      specific IgE or IgG levels. However, none of these are specific for ABPA,and there is still
      no consensus on the number of criteria needed for diagnosis, and patients in different stages
      of ABPA may not fulfill all these criteria. Also, there is no established definition for
      remission of ABPA. The most widely followed criteria are clinical and radiological
      improvement with at least 35 percent decline in total serum IgE levels. However, in a recent
      study the investigators demonstrated that a 35% decline in serum IgE levels at six weeks is
      not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE
      levels < 2500 IU/mL. Moreover, the quantum decline in serum IgE levels did not predict
      clinical outcome. The disorder is highly prevalent in India. The investigators have
      previously reported our experience with screening stable outpatients with bronchial asthma
      and acute severe asthma for ABPA. The investigators have also recently reported the
      prognostic factors associated with clinical outcomes in patients with ABPA.

      Oral corticosteroids are currently the treatment of choice for ABPA associated with bronchial
      asthma. They not only suppress the immune hyperfunction but are also anti-inflammatory.
      However, there is no data to guide the dose and duration of glucocorticoids and different
      regimens of glucocorticoids have been used in literature. Itraconazole, an oral triazole with
      relatively low toxicity, is active against Aspergillus spp. in vitro and in vivo. The
      activity of itraconazole against Aspergillus spp. is more than that of ketoconazole. The
      administration of itraconazole can eliminate Aspergillus in the airways and can theoretically
      reduce the allergic responses in ABPA. The aim of this prospective randomized controlled
      trial (RCT) is to evaluate the efficacy and safety of itraconazole monotherapy in patients
      with ABPA.
    

Intervention name(s): Glucocorticoids; Itraconazole
Intervention type(s): Drug; Drug
Intervention description(s): Prednisolone 0.5 mg/kg/day for 4 weeks; 0.25 mg/kg/day for 4 weeks; 0.125 mg/kg/day for 4 weeks. Then taper by 5 mg every 2 weeks and discontinue. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) as needed as per the SMART approach for control of asthma; Itraconazole 200 mg BD for 6 months along with inhaled formoterol/fluticasone (6/125 mcg) 2 puffs twice daily by MDI and as needed as per the SMART approach
Other intervention name(s): Prednisolone; Azole
Intervention MeSH terms: Itraconazole; Prednisolone; Glucocorticoids
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: ABPA