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

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

Study Overview

• Status: Completed
• Conditions: Allergic Bronchopulmonary Aspergillosis
• Intervention / Treatment: Drug: Inhaled budesonide; Drug: Inhaled amphotericin

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• India
  • Chandigarh, India, 160012
    • Chest clinic, PGIMER

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria: ABPA in remission defined as follows:

1. Age 12-65 years
2. Diagnosis of ABPA in the Chest Clinic
3. 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).
4. 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:

1. Failure to provide informed consent
2. Pregnancy
3. Involved in any other research protocol

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inhaled budesonide; 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; 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.
Experimental: Inhaled budesonide plus amphotericin; 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; 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.; Drug: Inhaled amphotericin; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: May 13, 2013
• First Submitted That Met QC Criteria: May 17, 2013
• First Posted (Estimate): May 20, 2013

Study Record Updates

• Last Update Posted (Estimate): August 5, 2015
• Last Update Submitted That Met QC Criteria: August 4, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: ABPA
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bacterial Infections and Mycoses; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Lung Diseases, Fungal; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Physiological Effects of Drugs; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Antifungal Agents; Antiprotozoal Agents; Antiparasitic Agents; Amebicides; Budesonide; Amphotericin B; Liposomal amphotericin B
• Other Study ID Numbers: NK/708/Res/181

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No