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Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis (MIPA)

Primary Purpose

Allergic Bronchopulmonary Aspergillosis

Status
Completed
Phase
Phase 2
Locations
India
Study Type
Interventional
Intervention
Glucocorticoids
Itraconazole
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Allergic Bronchopulmonary Aspergillosis focused on measuring ABPA

Eligibility Criteria

12 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Postgraduate Institute of Medical Education and Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Itraconazole group

Glucocorticoid group

Arm Description

Itraconazole 200 mg BD for 4 months along with inhaled formoterol/fluticasone (6/125 mcg) 2 puffs twice daily by MDI and as needed as per the SMART approach

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

Outcomes

Primary Outcome Measures

Remission rates in the two groups at six weeks and three months
Remission - if the IgE levels decline by >=25% and there is clinical improvement with partial/total clearance of chest radiographic lesions after three months of glucocorticoids (if previously present pulmonary opacities)
Percentage decline in IgE levels at six weeks and three months
IgE levels will be noted at baseline six weeks and three months after glucocorticoid therapy and percentage decline will be calculated as: (baseline IgE levels minus IgE levels after six weeks of treatment) divided by baseline IgE levels
Complete remission rates in the two groups
No ABPA exacerbations over the next 3 months after stopping therapy

Secondary Outcome Measures

Relapse rates in the two groups at six and 12 months after completion of treatment
Relapse - doubling of the baseline IgE levels irrespective of the patient's symptoms or appearance of radiologic infiltrates
Treatment related adverse effects in the two groups

Full Information

First Posted
March 23, 2011
Last Updated
March 15, 2017
Sponsor
Postgraduate Institute of Medical Education and Research
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1. Study Identification

Unique Protocol Identification Number
NCT01321827
Brief Title
Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis
Acronym
MIPA
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
April 2011 (undefined)
Primary Completion Date
March 2013 (Actual)
Study Completion Date
December 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Postgraduate Institute of Medical Education and Research

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Allergic Bronchopulmonary Aspergillosis
Keywords
ABPA

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Itraconazole group
Arm Type
Experimental
Arm Description
Itraconazole 200 mg BD for 4 months along with inhaled formoterol/fluticasone (6/125 mcg) 2 puffs twice daily by MDI and as needed as per the SMART approach
Arm Title
Glucocorticoid group
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Glucocorticoids
Other Intervention Name(s)
Prednisolone
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Itraconazole
Other Intervention Name(s)
Azole
Intervention Description
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
Primary Outcome Measure Information:
Title
Remission rates in the two groups at six weeks and three months
Description
Remission - if the IgE levels decline by >=25% and there is clinical improvement with partial/total clearance of chest radiographic lesions after three months of glucocorticoids (if previously present pulmonary opacities)
Time Frame
6 weeks, 3 months
Title
Percentage decline in IgE levels at six weeks and three months
Description
IgE levels will be noted at baseline six weeks and three months after glucocorticoid therapy and percentage decline will be calculated as: (baseline IgE levels minus IgE levels after six weeks of treatment) divided by baseline IgE levels
Time Frame
6 weeks, 3 months
Title
Complete remission rates in the two groups
Description
No ABPA exacerbations over the next 3 months after stopping therapy
Time Frame
3 months, 6 months
Secondary Outcome Measure Information:
Title
Relapse rates in the two groups at six and 12 months after completion of treatment
Description
Relapse - doubling of the baseline IgE levels irrespective of the patient's symptoms or appearance of radiologic infiltrates
Time Frame
6 months, 12 months
Title
Treatment related adverse effects in the two groups
Time Frame
Every 6 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ritesh Agarwal, MD, DM
Organizational Affiliation
PGIMER, Chandigarh
Official's Role
Principal Investigator
Facility Information:
Facility Name
Postgraduate Institute of Medical Education and Research
City
Chandigarh
State/Province
UT
ZIP/Postal Code
160012
Country
India

12. IPD Sharing Statement

Citations:
PubMed Identifier
29331473
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.
Results Reference
derived

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Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis

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