Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Azithromycin and Placebo for Azithromycin | Active Comparator | 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 |
|
| Placebo for Azithromycin | Placebo Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azithromycin | Drug | Azithromycin (C38H72N2O12 MW 749) is a 15-membered azalide, a subclass of macrolide antibiotics |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| ALBERT IRUTHIARAJ ANTHONY, MBBS | Penang Hospital, Malaysia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Respiratory Unit, Taiping Hospital | Taiping | Perak | 34000 | Malaysia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15813663 | Background | 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. | |
| 18653323 | Background | 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. |
Not provided
Not provided
12 subjects were excluded from randomization as they did not have chronic sputum production and were unable to perform spirometry.
A total of 90 subjects with a High Resolution CT scan diagnosis of pulmonary bronchiectasis was recruited from January - October 2011. Recruitment was done amongst patients in chest clinic, Hospital Taiping. A total of 78 subjects were selected based on the inclusion and exclusion criterias.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Azithromycin and Placebo for Azithromycin | Patients randomised to the treatment arm received 1000mg of azithromycin once a week for 12 weeks followed by placebo for azithromycin once a week for another 12 weeks. |
| FG001 | Placebo for Azithromycin | Patients randomised to the control arm received placebo for azithromycin once a week for 12 weeks followed by placebo for azithromycin once a week for another 12 weeks. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment vs. Placebo |
|
| |||||||||||||||||||||
| Control Phase |
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Azithromycin | Patients randomised to the treatment arm received 1000mg of azithromycin once a week for 12 weeks followed by placebo for azithromycin once a week for another 12 weeks. |
| BG001 | Placebo for Azithromycin |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | A total of 90 subjects were recruited. Among them, 78 subjects fulfilled the inclusion criteria and were randomized. Only 68 subjects completed the study and were subjected for analysis. We targeted to recruit 80 subjects and a dropout rate of 20% was anticipated as stated in the protocol. | Posted | Mean | Standard Deviation | gram | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
Subjects were monitored for adverse drug reactions for 24 weeks. Monitoring included enquiry of symptoms, physical examination and venous sampling at every visit.
Any clinically significant result outside normal ranges from these visits was documented and was reported as an adverse event. The subjects were withdrawn from the trial and then monitoring will continue until resolution or an appropriate medical judgment has been made to determine the cause and severity of the case.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Azithromycin | Patients randomised to the treatment arm received1000mg of azithromycin once a week for 12 weeks followed by placebo for azithromycin once a week for another 12 weeks. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia Hospitalisations | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment | The diarrhea resolved upon discontinuation of study treatment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Albert Iruthiaraj L. Anthony | Ministry of Health of Malaysia | +60174633410 | albert5409@yahoo.com |
Not provided
| ID | Term |
|---|---|
| D001987 | Bronchiectasis |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D017963 | Azithromycin |
| D013607 | Tablets |
| ID | Term |
|---|---|
| D004917 | Erythromycin |
| D018942 | Macrolides |
| D061065 | Polyketides |
| D007783 | Lactones |
| D009930 |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo for Azithromycin | Drug | 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. |
|
| 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) | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
| 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) | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
| 15170047 | Background | Davies G, Wilson R. Prophylactic antibiotic treatment of bronchiectasis with azithromycin. Thorax. 2004 Jun;59(6):540-1. No abstract available. |
| 25183304 | Derived | 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. |
| NOT COMPLETED |
|
|
Patients randomised to the control arm received placebo for azithromycin once a week for 12 weeks followed by placebo for azithromycin once a week for another 12 weeks.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Sputum volume | Higher sputum volume indicates active disease process and poorer morbidity. Lower sputum volume is associated with better control of disease process. | Mean | Standard Deviation | gram |
|
| St George's Respiratory Questionnaire (SGRQ) score | St George's Respiratory Questionnaire (SGRQ) score measures quality of life in patients with chronic lung disease. Score can range from 10 (minimum) until 100 (maximum). Lower scores are associated with good quality of life and the higher scores indicates poor quality of life. Total score is a product of summation of individual scores per question. | Mean | Standard Deviation | Scores on a scale |
|
| Forced Expiratory Volume at 1 second (FEV1) | Forced expiratory volume at 1 second (FEV1) is a reflection of lung volume. Higher values reflect less airflow limitation and good lung reserve. Lower values indicate poor airflow limitation and lower lung reserve. | Mean | Standard Deviation | Litres |
|
| Forced Vital Capacity (FVC) | Forced vital capacity (FVC) is a measurement of lung volume. Higher values reflect better reserve meanwhile lower values indicate poorer reserve. | Mean | Standard Deviation | Litres |
|
|
|
|
|
| Secondary | 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 | Posted | Mean | Standard Deviation | Units | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
|
|
|
|
| Secondary | 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) | Posted | Mean | Standard Deviation | Litres | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
|
|
|
|
| Secondary | 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) | Posted | Mean | Standard Deviation | Litres | Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24) |
|
|
|
|
| 5 |
| 33 |
| 3 |
| 33 |
| EG001 | Placebo for Azithromycin | Patients randomised to the control arm received placebo for azithromycin once a week for 12 weeks followed by placebo for azithromycin once a week for another 12 weeks. | 4 | 35 | 1 | 35 |
| Pneumonia Deaths | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
|
Not provided
Not provided
Not provided
| Organic Chemicals |
| D004304 | Dosage Forms |
| D004364 | Pharmaceutical Preparations |
| Visit 8(Week 24) |
|
SGRQ scores were compared between Visit 6 (Week 12) and Visit 3 (Baseline), Visit 8 (Week 24) and Visit 3 (Baseline), as well for Visit 8 (Week 24) and Visit 6 (Week 12). Independent t-test was applied for study end points which were numerical variables |
| t-test, 1 sided |
| <0.01 |
p valu of less than 0.05 was considered significant. |
| No |
| Superiority or Other |
| Visit 8(Week 24) |
|
FEV1 values were compared between Visit 6 (Week 12) and Visit 3 (Baseline), Visit 8 (Week 24) and Visit 3 (Baseline), as well for Visit 8 (Week 24) and Visit 6 (Week 12). Independent t-test was applied for study end points which were numerical variables. |
| t-test, 1 sided |
| <0.01 |
p value of less than 0.05 was considered significant |
| No |
| Superiority or Other |
| Visit 8(Week 24) |
|
FVC values were compared between Visit 6 (Week 12) and Visit 3 (Baseline), Visit 8 (Week 24) and Visit 3 (Baseline), as well for Visit 8 (Week 24) and Visit 6 (Week 12). Independent t-test was applied for study end points which were numerical variables. |
| t-test, 1 sided |
| <0.01 |
p value of less than 0.05 was considered significant. |
| No |
| Superiority or Other |