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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Ritesh Agarwal, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier:
NCT01857479
First received: May 13, 2013
Last updated: August 4, 2015
Last verified: August 2015
  Purpose
Inhaled amphotericin, a antifungal drug would decrease Aspergillus colonization and decrease the occurrence of exacerbations of Allergic Bronchopulmonary Aspergillosis (ABPA).

Condition Intervention Phase
Allergic Bronchopulmonary Aspergillosis
Drug: Inhaled budesonide
Drug: Inhaled amphotericin
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Postgraduate Institute of Medical Education and Research:

Primary Outcome Measures:
  • Time to first relapse [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Relapse will be defined as clinical and/or radiological worsening along with 50% increase of the baseline IgE levels


Secondary Outcome Measures:
  • ACQ-7 scores between the two groups [ Time Frame: 2, 4, 6, and 12 months ] [ Designated as safety issue: No ]
  • Number of asthma exacerbations requiring oral steroids [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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

  • Improvement in forced expiratory volume in the first second (FEV1) [ Time Frame: 2, 4, 6, and 12 months ] [ Designated as safety issue: No ]
  • Adverse effects of therapy in both the arms [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 21
Study Start Date: May 2013
Study Completion Date: June 2015
Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.


  Eligibility

Ages Eligible for Study:   12 Years to 65 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01857479

Locations
India
Chest Clinic, PGIMER
Chandigarh, India, 160012
Sponsors and Collaborators
Postgraduate Institute of Medical Education and Research
  More Information

Responsible Party: Ritesh Agarwal, Associate Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier: NCT01857479     History of Changes
Other Study ID Numbers: NK/708/Res/181 
Study First Received: May 13, 2013
Last Updated: August 4, 2015
Health Authority: India: DSMC, PGI Chandigarh

Keywords provided by Postgraduate Institute of Medical Education and Research:
ABPA

Additional relevant MeSH terms:
Aspergillosis
Pulmonary Aspergillosis
Aspergillosis, Allergic Bronchopulmonary
Hyalohyphomycosis
Dermatomycoses
Skin Diseases, Infectious
Infection
Mycoses
Skin Diseases
Lung Diseases, Fungal
Lung Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Respiratory Tract Infections
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Formoterol Fumarate
Budesonide
Amphotericin B
Liposomal amphotericin B
Amphotericin B, deoxycholate drug combination
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists

ClinicalTrials.gov processed this record on July 26, 2016