A Randomized Controlled Trial of Inhaled Amphotericin B for Maintaining Remission in Allergic Bronchopulmonary Aspergillosis

Study Overview
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Brief Summary
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Inhaled amphotericin, a antifungal drug would decrease Aspergillus colonization and decrease the occurrence of exacerbations of Allergic Bronchopulmonary Aspergillosis (ABPA).

Conditions
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Allergic Bronchopulmonary Aspergillosis

Intervention / Treatment
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* Drug: Inhaled budesonide
* Drug: Inhaled amphotericin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ABPA in remission defined as follows: Age 12-65 years Diagnosis of ABPA in the Chest Clinic Received glucocorticoids for management of ABPA according to the Chest clinic protocol (0.5 mg/kg/day for 4 weeks, 0.25 mg/kg/day for 4 weeks, 0.125 mg/kg/day for 4 weeks, subsequently taper and stop steroids over the next 4 weeks). Clinicoradiologic improvement with decline in IgE levels. The chest radiograph and IgE levels after four months of steroid therapy would serve as the baseline Exclusion Criteria: Failure to provide informed consent Pregnancy Involved in any other research protocol

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Inhaled budesonide<br>Nebulized budesonide 1 mg b.i.d. thrice a week for four months. Patients will also receive a metered dose inhaler of formoterol/budesonide (6/200) at a dose of 2 puffs b.i.d. and as and when required [max 10 puff/day] | Drug: Inhaled budesonide<br>* The control group will receive only nebulized budesonide 1 mg b.i.d. thrice a week for four months. Patients will also receive a metered dose inhaler of formoterol/budesonide (6/200) at a dose of 2 puffs b.i.d. and as and when required [max 10 puff/day]. The first dose will be administered under direct supervision. If the first dose is tolerated, therapy would be continued for the total duration of the study (4 months). The patient will be advised to clean the nebulizer chamber with soap and water after each administration to avoid contamination.<br>|
| Experimental: Inhaled budesonide plus amphotericin<br>Amphotericin B deoxycholate (50 mg) will be dissolved in 10 mL sterile water for injection (5 mg/mL). The solution remains stable for at least 7 days at 2°C to 8°C. Ten milligrams of the drug (2 mL) will be nebulized over 10-15 minutes twice in a day for three times a week (Effective dose: 10 mg b.i.d. thrice a week) using a jet nebulizer. Nebulized budesonide will be administered at a dose of 1 mg b.i.d. thrice a week after nebulization with amphotericin B. The total duration of therapy would last 4 months. Patients will also receive a metered dose inhaler of formoterol/budesonide (6/200) at a dose of 2 puffs b.i.d. and as and when required [max 10 puff/day]. The first dose will be administered under direct supervision. | Drug: Inhaled budesonide<br>* The control group will receive only nebulized budesonide 1 mg b.i.d. thrice a week for four months. Patients will also receive a metered dose inhaler of formoterol/budesonide (6/200) at a dose of 2 puffs b.i.d. and as and when required [max 10 puff/day]. The first dose will be administered under direct supervision. If the first dose is tolerated, therapy would be continued for the total duration of the study (4 months). The patient will be advised to clean the nebulizer chamber with soap and water after each administration to avoid contamination.<br>Drug: Inhaled amphotericin<br>* Amphotericin B deoxycholate (50 mg) will be dissolved in 10 mL sterile water for injection (5 mg/mL). The solution remains stable for at least 7 days at 2°C to 8°C. Ten milligrams of the drug (2 mL) will be nebulized over 10-15 minutes twice in a day for three times a week (Effective dose: 10 mg b.i.d. thrice a week) using a jet nebulizer. Nebulized budesonide will be administered at a dose of 1 mg b.i.d. thrice a week after nebulization with amphotericin B. The total duration of therapy would last 4 months. Patients will also receive a metered dose inhaler of formoterol/budesonide (6/200) at a dose of 2 puffs b.i.d. and as and when required [max 10 puff/day]. The first dose will be administered under direct supervision.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first relapse | Relapse will be defined as clinical and/or radiological worsening along with 50% increase of the baseline IgE levels | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACQ-7 scores between the two groups |  | 2, 4, 6, and 12 months | 
| Number of asthma exacerbations requiring oral steroids | During each exacerbation, chest radiograph and IgE levels will be performed; Asthma exacerbation will be defined as worsening asthma control without radiological changes consistent with ABPA exacerbation and absence of doubling of baseline IgE levels | 12 months | 
| Improvement in forced expiratory volume in the first second (FEV1) |  | 2, 4, 6, and 12 months | 
| Adverse effects of therapy in both the arms |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABPA