Overview

This trial is active, not recruiting.

Condition allergic bronchopulmonary aspergillosis
Treatments glucocorticoids, itraconazole
Phase phase 2/phase 3
Sponsor Postgraduate Institute of Medical Education and Research
Start date April 2011
End date March 2013
Trial size 50 participants
Trial identifier NCT01321827, IGCST, MS/1398/Res/1838

Summary

The purpose of this study is to evaluate the efficacy and safety of itraconazole monotherapy in patients with ABPA.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Itraconazole 200 mg BD for 6 months along with inhaled formoterol/fluticasone (6/125 mcg) 2 puffs twice daily by MDI and as needed as per the SMART approach
itraconazole Azole
Itraconazole 200 mg BD for 6 months along with inhaled formoterol/fluticasone (6/125 mcg) 2 puffs twice daily by MDI and as needed as per the SMART approach
(Active Comparator)
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 2 weeks and discontinue. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) as needed as per the SMART approach for control of asthma
glucocorticoids Prednisolone
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 2 weeks and discontinue. Patients will also receive inhaled formoterol/fluticasone (6/125 mcg) as needed as per the SMART approach for control of asthma

Primary Outcomes

Measure
Remission rates in the two groups at six weeks and three months
time frame: 6 weeks, 3 months
Percentage decline in IgE levels at six weeks and three months
time frame: 6 weeks, 3 months
Complete remission rates in the two groups
time frame: 3 months, 6 months

Secondary Outcomes

Measure
Relapse rates in the two groups at six and 12 months after completion of treatment
time frame: 6 months, 12 months
Treatment related adverse effects in the two groups
time frame: Every 6 weeks

Eligibility Criteria

Male or female participants from 12 years up to 70 years old.

Inclusion Criteria: Patients will be included in the study if they meet the criteria for ABPA defined by 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 kU/L Two of the following criteria: - presence of serum precipitating antibodies against A fumigatus - fixed or transient radiographic pulmonary opacities - absolute eosinophil count > 1000/µL - central bronchiectasis on HRCT. Exclusion Criteria: - if they have taken glucocorticoids for more than three weeks in the preceding six months - failure to give informed consent - enrollment in another trial of ABPA

Additional Information

Principal investigator Ritesh Agarwal, MD, DM
Description Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disorder caused by a complex hypersensitivity response to antigens released by the fungus Aspergillus fumigatus. The clinical entity was first described by Hinson et al in 1952, and the clinical and immunologic significance of Aspergillus fumigatus in the sputum were reported by Pepys and coworkers in 1959. The prevalence of ABPA in bronchial asthma is fairly high and a recent meta-analysis suggested the prevalence of ABPA in asthma clinics to be as high as 13 percent. Diagnostic criteria for ABPA have been laid and generally include the following eight major criteria: (a) history of asthma; (b) transient or fixed pulmonary infiltrates; (c) immediate cutaneous hyperreactivity to A fumigatus antigen; (d) absolute eosinophil count > 1000/µL; (e) serum precipitins against A fumigatus; (f) total IgE levels > 1000 IU/mL; (g) central bronchiectasis on high-resolution computed tomography (HRCT); and, (h) raised A fumigatus specific IgE or IgG levels. However, none of these are specific for ABPA,and there is still no consensus on the number of criteria needed for diagnosis, and patients in different stages of ABPA may not fulfill all these criteria. Also, there is no established definition for remission of ABPA. The most widely followed criteria are clinical and radiological improvement with at least 35 percent decline in total serum IgE levels. However, in a recent study the investigators demonstrated that a 35% decline in serum IgE levels at six weeks is not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE levels < 2500 IU/mL. Moreover, the quantum decline in serum IgE levels did not predict clinical outcome. The disorder is highly prevalent in India. The investigators have previously reported our experience with screening stable outpatients with bronchial asthma and acute severe asthma for ABPA. The investigators have also recently reported the prognostic factors associated with clinical outcomes in patients with ABPA. 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 aim of this prospective randomized controlled trial (RCT) is to evaluate the efficacy and safety of itraconazole monotherapy in patients with ABPA.
Trial information was received from ClinicalTrials.gov and was last updated in October 2015.
Information provided to ClinicalTrials.gov by Postgraduate Institute of Medical Education and Research.