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

Sponsor

Postgraduate Institute of Medical Education and Research (Other)

Overall Status

Unknown status

CT.gov ID

NCT02440009

Collaborator

(none)

150

Enrollment

Location

Arms

Duration (Months)

3.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Allergic Bronchopulmonary Aspergillosis	Drug: Itraconazole Drug: Glucocorticoids	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2015

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

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: Itraconazole Oral itraconazole 200 mg BD for 6 months Other Names: Azole 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

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: Itraconazole

Oral itraconazole 200 mg BD for 6 months

Other Names:

Azole

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

Outcome Measures

Primary Outcome Measures

Relapse rates [12 months]
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
Glucocorticoid-dependent ABPA [24 months]
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

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chest Clinic, PGIMER	Chandigarh		India	160012

Sponsors and Collaborators

Postgraduate Institute of Medical Education and Research

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Ritesh Agarwal, Professor, Department of Pulmonary Medicine, Principal Investigator, Postgraduate Institute of Medical Education and Research

ClinicalTrials.gov Identifier:

NCT02440009

Other Study ID Numbers:

Histo-15-IMEC-313

First Posted:

May 12, 2015

Last Update Posted:

Aug 23, 2018

Last Verified:

Aug 1, 2018

Additional relevant MeSH terms:

Aspergillosis

Pulmonary Aspergillosis

Aspergillosis, Allergic Bronchopulmonary

Itraconazole

Glucocorticoids

Study Results

No Results Posted as of Aug 23, 2018