Voriconazole Versus Oral Steroids in Allergic Bronchopulmonary Aspergillosis

Study Overview
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Brief Summary
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This is a research project to evaluate the efficacy and safety of two different treatment protocols in Allergic bronchopulmonary Aspergillosis.

Detailed Description
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Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by a complex hypersensitivity response to antigens released by the fungus Aspergillus fumigatus. The management of ABPA includes two important aspects - 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. 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 new triazoles, such as voriconazole, have recently been found effective in the treatment of fungal infections. The investigators hypothesize that voriconazole might also be useful in the treatment of ABPA. The aim of this prospective randomized controlled trial (RCT) is to evaluate the efficacy and safety of voriconazole therapy in patients with ABPA.

Official Title
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A Randomized Controlled Trial of Voriconazole in Allergic Bronchopulmonary Aspergillosis

Conditions
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Allergic Bronchopulmonary Aspergillosis

Intervention / Treatment
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* Drug: Prednisolone
* Drug: Voriconazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of all the following three criteria: Immediate cutaneous hyperreactivity on aspergillus skin test Elevated total IgE levels > 1000 IU/mL A fumigatus specific IgE levels > 0.35 kUA/L And, two of the following criteria: Presence of serum precipitating antibodies against A fumigatus Fixed or transient radiographic pulmonary opacities Total eosinophil count > 1000/µL Central bronchiectasis on HRCT Exclusion Criteria: Failure to give informed consent Intake of glucocorticoids for more than three weeks in the preceding six months Enrollment in another trial of ABPA Any exposure to azoles in the last six months

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 65 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Steroid group<br> | Drug: Prednisolone<br>* 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. 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<br>|
| Experimental: Voriconazole group<br> | Drug: Voriconazole<br>* Voriconazole 200 mg BD for 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<br>* Other names: Voritek 200 mg twice daily for four months;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rates in the two groups | IgE levels decline by >=25 percent and there is clinical improvement with partial/total clearance of chest radiographic lesions [if pulmonary opacities have been previously present] after six and three months of treatment | Six weeks and three months | 
| Relapse rates in the two groups | No ABPA exacerbations over the next 3 months after stopping therapy | 12, 18, 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events | Adverse events in the two groups | 4 months |