A Randomized Trial of Itraconazole in Acute Stages of Allergic Bronchopulmonary Aspergillosis (RIA)

Post Graduate Institute of Medical Education and Research, Chandigarh

Status and phase: Completed; Phase 3; Phase 2

Conditions: Allergic Bronchopulmonary Aspergillosis

Treatments: Drug: Itraconazole; Drug: Glucocorticoids

Study type: Interventional

Funder types: Other

Identifiers

NCT02440009

Histo-15-IMEC-313

Details and patient eligibility

About

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

Full description

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.

Enrollment: 191 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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191 participants in 2 patient groups

Glucocorticoid group

Active Comparator group

Description:

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

Treatment:

Drug: Glucocorticoids

Itraconazole plus glucocorticoid group

Experimental group

Description:

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.

Treatment:

Drug: Glucocorticoids

Drug: Itraconazole