Back to resultsEfficacy of Azithromycin in Treatment of Bronchiectasis
Primary Purpose
Bronchiectasis
Status
Completed
Phase
Phase 4
Locations
Malaysia
Study Type
Interventional
Intervention
Azithromycin
Placebo for Azithromycin
Sponsored by
About this trial
This is an interventional treatment trial for Bronchiectasis focused on measuring Azithromycin, Bronchiectasis, Macrolide, Inflammation, Pulmonary
Eligibility Criteria
Inclusion Criteria:
- Have provided written informed consent to participate in the study in accordance with the local ethics committee regulations
- Have a confirmed diagnosis of bronchiectasis (by HRCT) Aged 18 years or over Have chronic sputum production, defined as a greater than 45 mililitres volume produced in the 1 week prior to study entry.
- Be able to perform reproducible spirometry
- Be in a relatively stable disease state in the 6 weeks prior to entry, as defined by the absence of the following: respiratory exacerbations requiring hospitalisation, change in cough and/or sputum production, new or increased hemoptysis, more than 10% weight loss, use of additional antibiotic courses
Exclusion Criteria:
- Subjects will be excluded if one or more of the following criteria occur. The subject: Is an investigator, or an immediate family member of an investigator
- Has a confirmed diagnosis of cystic fibrosis, as evidenced by genetic analysis or a sweat test result more than 60mmol/L
- Has a primary immunodeficiency Is a pregnant or lactating female Has had a respiratory exacerbation requiring hospitalisation or additional course of antibiotics in the 6 weeks prior to study entry
- Has been prescribed or used oral steroids on any occasion for the 3 months prior to study entry.
- Has been using mucolytic agents on any occasion for the 2 months prior to study entry Has active tuberculosis
- Has an active malignancy, including melanoma (other skin carcinomas excluded)
- Has a history of significant liver disease or insufficiency Has a significant history of drug abuse (including alcohol abuse) or mental illness Has a known intolerance or allergy to macrolides
- Has been participating in another interventional drug study in the 3 months prior to enrolment into this study
Sites / Locations
- Respiratory Unit, Taiping Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Azithromycin and Placebo for Azithromycin
Placebo for Azithromycin
Arm Description
Patients randomised to the treatment arm are to receive 1000 mg of azithromycin once a week for 12 weeks followed by placebo for azithromycin once weekly for another 12 weeks
In Part One of the study participants will be randomised to receive 12 weeks of either placebo or azithromycin in a 1:1 ratio in a double-blinded fashion. After 12 weeks, in Part Two of the study, all participants will receive placebo in a double-blinded fashion for an additional 12 weeks.
Outcomes
Primary Outcome Measures
24 Hour Sputum Volume
Each participant must be instructed and enabled to collect 24 hour sputum volumes over the 24 hours prior to visits 3, 6 and 8, inclusive. As this is the primary endpoint of the study, it is critical that 24 hour sputum volumes are measured and recorded accurately, observing the following protocol: The subject should be given a sterile jar to collect the sputum, which has been weighed previously for convenience. Each jar will be labelled with subject name, start and finish time/date The collection should commence on rising in the morning and complete 24 hours later. Ensure that the sputum sample has minimal saliva in the collection Instruct subject to collect all sputum produced spontaneously or after coughing over a single daytime 24 hour period. The sample should come from the lungs and should not be salivary. Encourage subject not to swallow sputum, but to collect. Each 24 hour collection period should be as similar as possible in terms of physiotherapy and exercise regimens
Secondary Outcome Measures
Health Status: St George's Respiratory Questionnaire Score
The St. George Respiratory Questionnaire is to be administered at visits 3, 6 and 8 inclusive. It should be administered in a quiet room where the participant can answer the questions without interruption, prior to any other protocol related procedures
Spirometry Value; Forced Expiratory Volume at 1 Second (FEV1)
Pulmonary function testing using a spirometer will be carried out at visits 3, 6 and 8 inclusive. All testing should be done in the sitting position, except for obese patients, who commonly obtain deeper inspiration when tested in the standing position. Subjects should avoid the following prior to lung function testing: Smoking within 1 hour of testing Consuming alcohol within 4 hours of testing Performing vigorous exercise within 30 minutes of testing Wearing restrictive clothing around the chest or abdomen Eating a large meal within 2 hours of testing The following medications must be withheld prior to testing, with the minimum time from last dose indicated- short acting beta agonists (6 hours), long acting beta agonists (12 hours), ipratropium bromide (12 hours), antihistamines (12 hours), long acting bronchodilator combinations (12 hours)
Spirometric Values: Forced Vital Capacity (FVC)
Pulmonary function testing using a spirometer will be carried out at visits 3, 6 and 8 inclusive. All testing should be done in the sitting position, except for obese patients, who commonly obtain deeper inspiration when tested in the standing position. Subjects should avoid the following prior to lung function testing: Smoking within 1 hour of testing Consuming alcohol within 4 hours of testing Performing vigorous exercise within 30 minutes of testing Wearing restrictive clothing around the chest or abdomen Eating a large meal within 2 hours of testing The following medications must be withheld prior to testing, with the minimum time from last dose indicated- short acting beta agonists (6 hours), long acting beta agonists (12 hours), ipratropium bromide (12 hours), antihistamines (12 hours), Iong acting bronchodilator combinations (12 hours)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02107274
Brief Title
Efficacy of Azithromycin in Treatment of Bronchiectasis
Official Title
Efficacy of Azithromycin in Treatment of Bronchiectasis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
November 2011 (undefined)
Primary Completion Date
December 2013 (Actual)
Study Completion Date
December 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Penang Hospital, Malaysia
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Bronchiectasis is a chronic lung condition characterised primarily by dilatation of the airways. Only a small number of clinical studies have been conducted investigating the use of macrolides to treat non-cystic fibrosis bronchiectasis. The purpose of this study is to determine the efficacy of 12 weeks treatment with azithromycin in adult patients with non-cystic fibrosis bronchiectasis.
Detailed Description
Previous studies of various macrolides with small sample sizes have reported some benefit with the reduction of sputum volume in bronchiectasis patients. However, macrolide therapy could not yet be confidently used to treat bronchiectasis, given the diffuse nature of these findings. These studies have had a wide range of hypotheses, and have not necessarily focused on the anti-inflammatory effects of macrolides. Furthermore, these studies are few in number, and not all have been placebo-controlled or double-blinded. This, combined with the small sample sizes used, limits the reliability of these results. This study aims to expand on these limited published findings by investigating a larger sample population with different endpoints. Sputum volume and quality of life have been selected as important variables to aid in assessing efficacy.
This study aims to be independent of previous studies in a number of ways. This is the only study of bronchiectasis patients to formally investigate quality of life after treatment with a macrolide, and the potential carryover effect of azithromycin therapy. This study will also expand on the findings of previous studies of macrolides in bronchiectasis by incorporating a larger sample size into the trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiectasis
Keywords
Azithromycin, Bronchiectasis, Macrolide, Inflammation, Pulmonary
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
78 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Azithromycin and Placebo for Azithromycin
Arm Type
Active Comparator
Arm Description
Patients randomised to the treatment arm are to receive 1000 mg of azithromycin once a week for 12 weeks followed by placebo for azithromycin once weekly for another 12 weeks
Arm Title
Placebo for Azithromycin
Arm Type
Placebo Comparator
Arm Description
In Part One of the study participants will be randomised to receive 12 weeks of either placebo or azithromycin in a 1:1 ratio in a double-blinded fashion. After 12 weeks, in Part Two of the study, all participants will receive placebo in a double-blinded fashion for an additional 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Azithromycin
Other Intervention Name(s)
Zithromax 250 mg tablet
Intervention Description
Azithromycin (C38H72N2O12 MW 749) is a 15-membered azalide, a subclass of macrolide antibiotics
Intervention Type
Drug
Intervention Name(s)
Placebo for Azithromycin
Intervention Description
In Part One of the study participants will be randomised to receive 12 weeks of either placebo or azithromycin in a 1:1 ratio in a double-blinded fashion. After 12 weeks, in Part Two of the study, all participants will receive placebo in a double-blinded fashion for an additional 12 weeks.
Primary Outcome Measure Information:
Title
24 Hour Sputum Volume
Description
Each participant must be instructed and enabled to collect 24 hour sputum volumes over the 24 hours prior to visits 3, 6 and 8, inclusive. As this is the primary endpoint of the study, it is critical that 24 hour sputum volumes are measured and recorded accurately, observing the following protocol: The subject should be given a sterile jar to collect the sputum, which has been weighed previously for convenience. Each jar will be labelled with subject name, start and finish time/date The collection should commence on rising in the morning and complete 24 hours later. Ensure that the sputum sample has minimal saliva in the collection Instruct subject to collect all sputum produced spontaneously or after coughing over a single daytime 24 hour period. The sample should come from the lungs and should not be salivary. Encourage subject not to swallow sputum, but to collect. Each 24 hour collection period should be as similar as possible in terms of physiotherapy and exercise regimens
Time Frame
Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)
Secondary Outcome Measure Information:
Title
Health Status: St George's Respiratory Questionnaire Score
Description
The St. George Respiratory Questionnaire is to be administered at visits 3, 6 and 8 inclusive. It should be administered in a quiet room where the participant can answer the questions without interruption, prior to any other protocol related procedures
Time Frame
Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)
Title
Spirometry Value; Forced Expiratory Volume at 1 Second (FEV1)
Description
Pulmonary function testing using a spirometer will be carried out at visits 3, 6 and 8 inclusive. All testing should be done in the sitting position, except for obese patients, who commonly obtain deeper inspiration when tested in the standing position. Subjects should avoid the following prior to lung function testing: Smoking within 1 hour of testing Consuming alcohol within 4 hours of testing Performing vigorous exercise within 30 minutes of testing Wearing restrictive clothing around the chest or abdomen Eating a large meal within 2 hours of testing The following medications must be withheld prior to testing, with the minimum time from last dose indicated- short acting beta agonists (6 hours), long acting beta agonists (12 hours), ipratropium bromide (12 hours), antihistamines (12 hours), long acting bronchodilator combinations (12 hours)
Time Frame
Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)
Title
Spirometric Values: Forced Vital Capacity (FVC)
Description
Pulmonary function testing using a spirometer will be carried out at visits 3, 6 and 8 inclusive. All testing should be done in the sitting position, except for obese patients, who commonly obtain deeper inspiration when tested in the standing position. Subjects should avoid the following prior to lung function testing: Smoking within 1 hour of testing Consuming alcohol within 4 hours of testing Performing vigorous exercise within 30 minutes of testing Wearing restrictive clothing around the chest or abdomen Eating a large meal within 2 hours of testing The following medications must be withheld prior to testing, with the minimum time from last dose indicated- short acting beta agonists (6 hours), long acting beta agonists (12 hours), ipratropium bromide (12 hours), antihistamines (12 hours), Iong acting bronchodilator combinations (12 hours)
Time Frame
Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Have provided written informed consent to participate in the study in accordance with the local ethics committee regulations
Have a confirmed diagnosis of bronchiectasis (by HRCT) Aged 18 years or over Have chronic sputum production, defined as a greater than 45 mililitres volume produced in the 1 week prior to study entry.
Be able to perform reproducible spirometry
Be in a relatively stable disease state in the 6 weeks prior to entry, as defined by the absence of the following: respiratory exacerbations requiring hospitalisation, change in cough and/or sputum production, new or increased hemoptysis, more than 10% weight loss, use of additional antibiotic courses
Exclusion Criteria:
Subjects will be excluded if one or more of the following criteria occur. The subject: Is an investigator, or an immediate family member of an investigator
Has a confirmed diagnosis of cystic fibrosis, as evidenced by genetic analysis or a sweat test result more than 60mmol/L
Has a primary immunodeficiency Is a pregnant or lactating female Has had a respiratory exacerbation requiring hospitalisation or additional course of antibiotics in the 6 weeks prior to study entry
Has been prescribed or used oral steroids on any occasion for the 3 months prior to study entry.
Has been using mucolytic agents on any occasion for the 2 months prior to study entry Has active tuberculosis
Has an active malignancy, including melanoma (other skin carcinomas excluded)
Has a history of significant liver disease or insufficiency Has a significant history of drug abuse (including alcohol abuse) or mental illness Has a known intolerance or allergy to macrolides
Has been participating in another interventional drug study in the 3 months prior to enrolment into this study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ALBERT IRUTHIARAJ ANTHONY, MBBS
Organizational Affiliation
Penang Hospital, Malaysia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Respiratory Unit, Taiping Hospital
City
Taiping
State/Province
Perak
ZIP/Postal Code
34000
Country
Malaysia
12. IPD Sharing Statement
Citations:
PubMed Identifier
15813663
Citation
Cymbala AA, Edmonds LC, Bauer MA, Jederlinic PJ, May JJ, Victory JM, Amsden GW. The disease-modifying effects of twice-weekly oral azithromycin in patients with bronchiectasis. Treat Respir Med. 2005;4(2):117-22. doi: 10.2165/00151829-200504020-00005.
Results Reference
background
PubMed Identifier
18653323
Citation
Anwar GA, Bourke SC, Afolabi G, Middleton P, Ward C, Rutherford RM. Effects of long-term low-dose azithromycin in patients with non-CF bronchiectasis. Respir Med. 2008 Oct;102(10):1494-6. doi: 10.1016/j.rmed.2008.06.005. Epub 2008 Jul 23.
Results Reference
background
PubMed Identifier
15170047
Citation
Davies G, Wilson R. Prophylactic antibiotic treatment of bronchiectasis with azithromycin. Thorax. 2004 Jun;59(6):540-1. No abstract available.
Results Reference
background
PubMed Identifier
25183304
Citation
Lourdesamy Anthony AI, Muthukumaru U. Efficacy of azithromycin in the treatment of bronchiectasis. Respirology. 2014 Nov;19(8):1178-82. doi: 10.1111/resp.12375. Epub 2014 Sep 2.
Results Reference
derived
Learn more about this trial
Efficacy of Azithromycin in Treatment of Bronchiectasis
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