Allergic Bronchopulmonary AspergillosisPhase 2/3MIPANCT01321827
Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis
A Phase 2/3 study testing Glucocorticoids and Itraconazole in people with Allergic Bronchopulmonary Aspergillosis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
The purpose of this study is to evaluate the efficacy and safety of itraconazole monotherapy in patients with ABPA. Read more about this study
- Who is it for?
- Ages 12 to 70 years
- Conditions the study is for
- Allergic Bronchopulmonary Aspergillosis
- What is being tested?
- Glucocorticoids and Itraconazole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteIndia
- Study dates
- Apr 2011to Dec 2015
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
India1 site
Postgraduate Institute of Medical Education and Research
Chandigarh, Uttarakhand, 160012
About this study
The purpose of this study is to evaluate the efficacy and safety of itraconazole monotherapy in patients with ABPA.
Read the 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.
- Conditions
- Allergic Bronchopulmonary Aspergillosis
- Being tested
- Glucocorticoids, Itraconazole
- Keywords
- ABPA
- Medical subject headings
- Aspergillosis, Allergic Bronchopulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlucocorticoidsDrug
Also called 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
ItraconazoleDrug
Also called 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
| Study group | Role | What they receive |
|---|---|---|
| Itraconazole group | Experimental | 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 Receives: Drug: Itraconazole |
| Glucocorticoid group | 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 Receives: Drug: Glucocorticoids |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 weeks, 3 months
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
Measured: 6 weeks, 3 months
Complete remission rates in the two groups
No ABPA exacerbations over the next 3 months after stopping therapy
Measured: 3 months, 6 months
Secondary outcomes (2)
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
Measured: 6 months, 12 months
Treatment related adverse effects in the two groups
Measured: Every 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2011 (estimated)
- Study startApr 2011
- Primary completionMar 2013
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Allergic Bronchopulmonary AspergillosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ritesh Agarwal, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Ritesh Agarwal, MD, DM, Principal investigator, PGIMER, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01321827
- Sponsor's protocol ID
- IGCST
- Other IDs
- MS/1398/Res/1838
- Acronym
- MIPA
- Status last verified
- Mar 2017
- First submitted
- 23 Mar 2011
- Last updated
- 16 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 29331473
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Monotherapy of Itraconazole Versus Prednisolone in Allergic Bronchopulmonary Aspergillosis
- ClinicalTrials.gov ID
- NCT01321827
- Acronym / sponsor ID
- MIPA / IGCST
- Conditions
- Allergic Bronchopulmonary Aspergillosis
- Keywords
- ABPA
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- Apr 2011
- Primary completion
- Mar 2013 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 24 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Itraconazole group | Experimental | Drug: ItraconazoleItraconazole 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 |
| Glucocorticoid group | Active comparator | Drug: GlucocorticoidsPrednisolone 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 |
Who may qualify
- Ages
- 12 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlucocorticoidsAlso: PrednisolonePrednisolone 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 | Drug | Glucocorticoid group |
| ItraconazoleAlso: AzoleItraconazole 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 | Drug | Itraconazole group |
Primary outcome
Remission rates in the two groups at six weeks and three months
Time frame: 6 weeks, 3 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
Time frame: 6 weeks, 3 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
Time frame: 3 months, 6 months
No ABPA exacerbations over the next 3 months after stopping therapy
2 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Mar 2017.
- Derived from this study: PubMed 29331473Agarwal 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.
Related trials for Allergic Bronchopulmonary Aspergillosis
Not yet recruiting
Real-World Effectiveness of Depemokimab in Allergic Bronchopulmonary Aspergillosis With Severe Eosinophilic Asthma
Allergic Bronchopulmonary Aspergillosis, ABPA
RecruitingObservational study
T2AIR: Real-World Efficacy and Safety of Biologics Targeting Type 2 Inflammation in Asthma and COPD
Asthma, COPD (Chronic Obstructive Pulmonary Disease)
Not yet recruiting
Real-World Effectiveness of Tezepelumab in Allergic Bronchopulmonary Aspergillosis
Allergic Bronchopulmonary Aspergillosis, Severe Asthma
RecruitingObservational study
ML-Based ABPA Recurrence Prediction and Clinical Utility
ABPA, Allergic Bronchopulmonary Aspergillosis
RecruitingObservational study
Fungal Status and Prognosis in ABPA
ABPA, Allergic Bronchopulmonary Aspergillosis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ritesh Agarwal, MD, DM principal investigator
PGIMER, Chandigarh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Glucocorticoids and Itraconazole in people with Allergic Bronchopulmonary Aspergillosis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Remission rates in the two groups at six weeks and three months (time frame: 6 weeks, 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01321827, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Mar 2017.