A Randomized Trial of Itraconazole in Acute Stages of Allergic Bronchopulmonary Aspergillosis

Study Overview
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Brief Summary
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The study evaluates the addition of itraconazole to glucocorticoids in management of acute stages of allergic bronchopulmonary aspergillosis (ABPA). Half of the participants will receive glucocorticoids while the other half will receive itraconazole and glucocorticoids

Detailed Description
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The management of allergic bronchopulmonary aspergillosis (ABPA) includes two important aspects namely institution of immunosuppressive therapy in the form of glucocorticoids to control the immunologic activity, and close monitoring for detection of relapses. Another possible target is to use antifungal agents to attenuate the fungal burden secondary to the fungal colonization in the airways. 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. 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. We hypothesize that itraconazole when given in the acute stages of ABPA will decrease the chances of relapse and progression to glucocorticoid-dependent ABPA.

Official Title
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A Randomized Trial of Itraconazole in Acute Stages of Allergic Bronchopulmonary Aspergillosis

Conditions
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Allergic Bronchopulmonary Aspergillosis

Intervention / Treatment
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* Drug: Itraconazole
* Drug: Glucocorticoids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment naive patients of allergic bronchopulmonary aspergillosis (ABPA) defined by the presence of all the following: asthma immediate cutaneous hyperreactivity on Aspergillus skin test or A.fumigatus specific IgE levels >0.35 kUA/L elevated total IgE levels >1000 IU/mL and, two of the following features: presence of precipitating antibodies against A.fumigatus in serum fixed or transient radiographic pulmonary opacities total eosinophil count >1000/µL bronchiectasis on HRCT chest Exclusion Criteria: Intake of systemic glucocorticoids for more than three weeks in the preceding six months Exposure to azoles in the last six months Immunosuppressive states such as uncontrolled diabetes mellitus, chronic renal failure, chronic liver failure and others Patient on immunosuppressive drugs Pregnancy Enrollment in another trial of ABPA Failure to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glucocorticoid group<br>Oral 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 4 weeks and discontinue by the end of 4 months. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) 1 puff BD and as needed as per the SMART approach for control of asthma | Drug: Glucocorticoids<br>* Oral 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 4 weeks and discontinue by the end of 4 months.<br>* Other names: Steroid;|
| Experimental: Itraconazole plus glucocorticoid group<br>Oral itraconazole 200 mg BD for 6 months AND oral 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 4 weeks and discontinue by the end of 4 months. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) 1 puff BD and as needed as per the SMART approach for control of asthma. | Drug: Itraconazole<br>* Oral itraconazole 200 mg BD for 6 months<br>* Other names: Azole;Drug: Glucocorticoids<br>* Oral 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 4 weeks and discontinue by the end of 4 months.<br>* Other names: Steroid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relapse rates | Doubling of the baseline IgE levels irrespective of the patient's symptoms or appearance of radiologic infiltrates; or clinical and/or radiological worsening with 50% increase in IgE over the previous baseline value | 12 months | 
| Glucocorticoid-dependent ABPA | If the patient has relapse on two or more consecutive occasions within 6 months of stopping treatment or requires oral steroids for control of asthma | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with a response rates |  | Six weeks | 
| Percentage decline in IgE |  | Six weeks | 
| Time to first relapse |  | Two years | 
| Treatment-related adverse effects |  | Six months |