Trial Outcomes & Findings for Efficacy of Azithromycin in Treatment of Bronchiectasis (NCT NCT02107274)
NCT ID: NCT02107274
Last Updated: 2014-07-18
Results Overview
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
COMPLETED
PHASE4
78 participants
Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)
2014-07-18
Participant Flow
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.
12 subjects were excluded from randomization as they did not have chronic sputum production and were unable to perform spirometry.
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Treatment vs. Placebo
STARTED
|
39
|
39
|
|
Treatment vs. Placebo
COMPLETED
|
36
|
37
|
|
Treatment vs. Placebo
NOT COMPLETED
|
3
|
2
|
|
Control Phase
STARTED
|
36
|
37
|
|
Control Phase
COMPLETED
|
33
|
35
|
|
Control Phase
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
|---|---|---|
|
Treatment vs. Placebo
Adverse Event
|
3
|
0
|
|
Treatment vs. Placebo
Lost to Follow-up
|
0
|
2
|
|
Control Phase
Lost to Follow-up
|
1
|
1
|
|
Control Phase
Death
|
2
|
0
|
|
Control Phase
Adverse Event
|
0
|
1
|
Baseline Characteristics
Efficacy of Azithromycin in Treatment of Bronchiectasis
Baseline characteristics by cohort
| Measure |
Azithromycin
n=33 Participants
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.
|
Placebo for Azithromycin
n=35 Participants
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.
|
Total
n=68 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.9 years
STANDARD_DEVIATION 11.77 • n=5 Participants
|
59.7 years
STANDARD_DEVIATION 15.03 • n=7 Participants
|
62.8 years
STANDARD_DEVIATION 13.4 • n=5 Participants
|
|
Sex: Female, Male
Female
|
18 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
40 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
28 Participants
n=5 Participants
|
|
Sputum volume
|
41.8 gram
STANDARD_DEVIATION 26.05 • n=5 Participants
|
23.6 gram
STANDARD_DEVIATION 20.67 • n=7 Participants
|
32.4 gram
STANDARD_DEVIATION 24.99 • n=5 Participants
|
|
St George's Respiratory Questionnaire (SGRQ) score
|
41.06 Scores on a scale
STANDARD_DEVIATION 9.95 • n=5 Participants
|
36.40 Scores on a scale
STANDARD_DEVIATION 10.59 • n=7 Participants
|
38.66 Scores on a scale
STANDARD_DEVIATION 10.47 • n=5 Participants
|
|
Forced Expiratory Volume at 1 second (FEV1)
|
1.08 Litres
STANDARD_DEVIATION 0.41 • n=5 Participants
|
1.17 Litres
STANDARD_DEVIATION 0.54 • n=7 Participants
|
1.13 Litres
STANDARD_DEVIATION 0.48 • n=5 Participants
|
|
Forced Vital Capacity (FVC)
|
1.56 Litres
STANDARD_DEVIATION 0.65 • n=5 Participants
|
1.69 Litres
STANDARD_DEVIATION 0.74 • n=7 Participants
|
1.63 Litres
STANDARD_DEVIATION 0.70 • n=5 Participants
|
PRIMARY outcome
Timeframe: Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)Population: 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.
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
Outcome measures
| Measure |
Azithromycin
n=33 Participants
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.
|
Placebo for Azithromycin
n=35 Participants
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.
|
|---|---|---|
|
24 Hour Sputum Volume
Visit 3(Baseline)
|
41.8 gram
Standard Deviation 26.1
|
23.6 gram
Standard Deviation 20.7
|
|
24 Hour Sputum Volume
Visit 6(Week 12)
|
29.9 gram
Standard Deviation 19.4
|
26.2 gram
Standard Deviation 20.5
|
|
24 Hour Sputum Volume
Visit 8(Week 24)
|
30.4 gram
Standard Deviation 20.6
|
28.5 gram
Standard Deviation 21.6
|
SECONDARY outcome
Timeframe: Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)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
Outcome measures
| Measure |
Azithromycin
n=33 Participants
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.
|
Placebo for Azithromycin
n=35 Participants
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.
|
|---|---|---|
|
Health Status: St George's Respiratory Questionnaire Score
Visit 6(Week 12)
|
30.2 Units
Standard Deviation 8.5
|
39.1 Units
Standard Deviation 9.3
|
|
Health Status: St George's Respiratory Questionnaire Score
Visit 3(Baseline)
|
41.1 Units
Standard Deviation 9.9
|
36.4 Units
Standard Deviation 10.6
|
|
Health Status: St George's Respiratory Questionnaire Score
Visit 8(Week 24)
|
31.7 Units
Standard Deviation 8.1
|
41.1 Units
Standard Deviation 11.1
|
SECONDARY outcome
Timeframe: Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)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)
Outcome measures
| Measure |
Azithromycin
n=33 Participants
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.
|
Placebo for Azithromycin
n=35 Participants
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.
|
|---|---|---|
|
Spirometry Value; Forced Expiratory Volume at 1 Second (FEV1)
Visit 3(Baseline)
|
1.08 Litres
Standard Deviation 0.41
|
1.17 Litres
Standard Deviation 0.55
|
|
Spirometry Value; Forced Expiratory Volume at 1 Second (FEV1)
Visit 6(Week 12)
|
1.09 Litres
Standard Deviation 0.40
|
1.10 Litres
Standard Deviation 0.53
|
|
Spirometry Value; Forced Expiratory Volume at 1 Second (FEV1)
Visit 8(Week 24)
|
1.04 Litres
Standard Deviation 0.37
|
1.08 Litres
Standard Deviation 0.49
|
SECONDARY outcome
Timeframe: Visit 3 (Baseline); Visit 6 (Week 12); Visit 8 (Week 24)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)
Outcome measures
| Measure |
Azithromycin
n=33 Participants
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.
|
Placebo for Azithromycin
n=35 Participants
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.
|
|---|---|---|
|
Spirometric Values: Forced Vital Capacity (FVC)
Visit 3(Baseline)
|
1.56 Litres
Standard Deviation 0.65
|
1.69 Litres
Standard Deviation 0.74
|
|
Spirometric Values: Forced Vital Capacity (FVC)
Visit 6(Week 12)
|
1.58 Litres
Standard Deviation 0.63
|
1.60 Litres
Standard Deviation 0.70
|
|
Spirometric Values: Forced Vital Capacity (FVC)
Visit 8(Week 24)
|
1.55 Litres
Standard Deviation 0.66
|
1.58 Litres
Standard Deviation 0.72
|
Adverse Events
Azithromycin
Placebo for Azithromycin
Serious adverse events
| Measure |
Azithromycin
n=33 participants at risk
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.
|
Placebo for Azithromycin
n=35 participants at risk
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.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Hospitalisations
|
9.1%
3/33 • Number of events 3 • 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.
|
11.4%
4/35 • Number of events 4 • 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.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia Deaths
|
6.1%
2/33 • Number of events 2 • 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.
|
0.00%
0/35 • 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.
|
Other adverse events
| Measure |
Azithromycin
n=33 participants at risk
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.
|
Placebo for Azithromycin
n=35 participants at risk
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.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
9.1%
3/33 • Number of events 3 • 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.
|
2.9%
1/35 • Number of events 1 • 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.
|
Additional Information
Dr. Albert Iruthiaraj L. Anthony
Ministry of Health of Malaysia
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place