Clinical trial NCT01321827: Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Allergic Bronchopulmonary Aspergillosis
Keywords: ABPA
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2011-03-24
Enrollment: 100
Sex: ALL
Minimum age (years): 12
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Remission rates in the two groups at six weeks and three months
timeFrame: 6 weeks, 3 months
measure: Percentage decline in IgE levels at six weeks and three months
timeFrame: 6 weeks, 3 months
measure: Complete remission rates in the two groups
timeFrame: 3 months, 6 months
Secondary outcomes:
measure: Relapse rates in the two groups at six and 12 months after completion of treatment
timeFrame: 6 months, 12 months
measure: Treatment related adverse effects in the two groups
timeFrame: Every 6 weeks
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
state: UT
Study officials:
affiliation: PGIMER, Chandigarh
name: Ritesh Agarwal, MD, DM
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agarwal R, Dhooria S, Singh Sehgal I, Aggarwal AN, Garg M, Saikia B, Behera D, Chakrabarti A. A Randomized Trial of Itraconazole vs Prednisolone in Acute-Stage Allergic Bronchopulmonary Aspergillosis Complicating Asthma. Chest. 2018 Mar;153(3):656-664. doi: 10.1016/j.chest.2018.01.005. Epub 2018 Jan 11.