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

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

Study Overview

• Status: Completed
• Conditions: Allergic Bronchopulmonary Aspergillosis
• Intervention / Treatment: Drug: Glucocorticoids; Drug: Itraconazole

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 191
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Chest clinic, PGIMER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glucocorticoid group; 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; 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.; Other Names: Steroid
Experimental: Itraconazole plus glucocorticoid group; 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: Glucocorticoids; 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.; Other Names: Steroid; Drug: Itraconazole; Oral itraconazole 200 mg BD for 6 months; Other Names: Azole

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): July 1, 2017
• Study Completion (Actual): July 31, 2017

Study Registration Dates

• First Submitted: May 1, 2015
• First Submitted That Met QC Criteria: May 6, 2015
• First Posted (Estimate): May 12, 2015

Study Record Updates

• Last Update Posted (Actual): October 7, 2022
• Last Update Submitted That Met QC Criteria: October 5, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bacterial Infections and Mycoses; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Lung Diseases, Fungal; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Antifungal Agents; Steroid Synthesis Inhibitors; 14-alpha Demethylase Inhibitors; Itraconazole; Glucocorticoids
• Other Study ID Numbers: Histo-15-IMEC-313