Trial Outcomes & Findings for A 1-year Multi-center, Prospective, Cohort Study in Patients With Chronic Obstructive Pulmonary Disease Treated With Long-acting Bronchodilator (NCT NCT01794780)
NCT ID: NCT01794780
Last Updated: 2019-09-26
Results Overview
Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. A positive change from baseline in FEV1 indicates improvement in lung function. Pulmonary function tests were performed at study visits including FEV1, and Force Vital Capacity (FVC). These were performed 30 minutes before treatment and not more than 2 hours in advance after stopping the Long-acting bronchodilators eight hours before visits. In order to reduce the variation between each test, the same instrument was used in the whole research process if condition allowed.
COMPLETED
PHASE4
2229 participants
Baseline,3 months
2019-09-26
Participant Flow
A total of 2253 patients entered into the database, of which 24 patients were exclude during the data review meetings, because they did not met the inclusion/exclusion criteria. Hence a total of 2229 patients enrolled successfully.
Participant milestones
| Measure |
Indacaterol
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium Bromide
LAMA: Tiotropium Bromide, once a day, 18 μg
|
Salmeterol/Fluticasone
LABA/ICS: Salmeterol/Fluticasone, twice a day, 50/250 μg, 50/500 μg
|
Budesonide/ Formoterol
Budesonide/formoterol, twice daily, two suction each time, 160/4.5 μg
|
Indacaterol +Tiotropium
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS (Or Budesonide/ Formoterol)+ Tiotropium
Salmeterol / fluticasone Or budesonide / formoterol
|
Oral Theophylline
Oral theophylline
|
Other Treatment
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
NOT COMPLETED
|
17
|
96
|
242
|
83
|
3
|
180
|
42
|
9
|
|
Overall Study
STARTED
|
32
|
276
|
813
|
283
|
9
|
632
|
154
|
30
|
|
Overall Study
COMPLETED
|
15
|
180
|
571
|
200
|
6
|
452
|
112
|
21
|
Reasons for withdrawal
| Measure |
Indacaterol
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium Bromide
LAMA: Tiotropium Bromide, once a day, 18 μg
|
Salmeterol/Fluticasone
LABA/ICS: Salmeterol/Fluticasone, twice a day, 50/250 μg, 50/500 μg
|
Budesonide/ Formoterol
Budesonide/formoterol, twice daily, two suction each time, 160/4.5 μg
|
Indacaterol +Tiotropium
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS (Or Budesonide/ Formoterol)+ Tiotropium
Salmeterol / fluticasone Or budesonide / formoterol
|
Oral Theophylline
Oral theophylline
|
Other Treatment
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
2
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Death
|
0
|
2
|
14
|
1
|
0
|
9
|
4
|
0
|
|
Overall Study
Lost to Follow-up
|
10
|
64
|
165
|
53
|
2
|
99
|
30
|
5
|
|
Overall Study
Withdrew informed consent
|
7
|
17
|
36
|
9
|
0
|
48
|
4
|
3
|
|
Overall Study
Other
|
0
|
12
|
25
|
20
|
1
|
24
|
4
|
1
|
Baseline Characteristics
A 1-year Multi-center, Prospective, Cohort Study in Patients With Chronic Obstructive Pulmonary Disease Treated With Long-acting Bronchodilator
Baseline characteristics by cohort
| Measure |
Indacaterol
n=32 Participants
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium Bromide
n=276 Participants
LAMA: Tiotropium Bromide, once a day, 18 μg
|
Salmeterol/Fluticasone
n=813 Participants
LABA/ICS: Salmeterol/Fluticasone, twice a day, 50/250 μg, 50/500 μg
|
Budesonide/ Formoterol
n=283 Participants
Budesonide/formoterol, twice daily, two suction each time, 160/4.5 μg
|
Indacaterol +Tiotropium
n=9 Participants
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS (Or Budesonide/ Formoterol)+ Tiotropium
n=632 Participants
Salmeterol / fluticasone Or budesonide / formoterol
|
Oral Theophylline
n=154 Participants
Oral theophylline
|
Other Treatment
n=30 Participants
|
Total
n=2229 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
66.12 Years
STANDARD_DEVIATION 9.238 • n=93 Participants
|
68.93 Years
STANDARD_DEVIATION 9.145 • n=4 Participants
|
67.00 Years
STANDARD_DEVIATION 9.353 • n=27 Participants
|
67.02 Years
STANDARD_DEVIATION 9.858 • n=483 Participants
|
69.49 Years
STANDARD_DEVIATION 8.873 • n=36 Participants
|
67.74 Years
STANDARD_DEVIATION 9.427 • n=10 Participants
|
67.86 Years
STANDARD_DEVIATION 9.652 • n=115 Participants
|
66.14 Years
STANDARD_DEVIATION 10.205 • n=40 Participants
|
67.50 Years
STANDARD_DEVIATION 9.453 • n=8 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=93 Participants
|
52 Participants
n=4 Participants
|
154 Participants
n=27 Participants
|
49 Participants
n=483 Participants
|
1 Participants
n=36 Participants
|
81 Participants
n=10 Participants
|
35 Participants
n=115 Participants
|
5 Participants
n=40 Participants
|
378 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=93 Participants
|
224 Participants
n=4 Participants
|
659 Participants
n=27 Participants
|
234 Participants
n=483 Participants
|
8 Participants
n=36 Participants
|
551 Participants
n=10 Participants
|
119 Participants
n=115 Participants
|
25 Participants
n=40 Participants
|
1851 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Baseline,3 monthsPopulation: FAS: Two Arms/Groups were grouped together in the analysis as some of the analysis required to combine the results. Per protocol it was not the intent to compare the results between different standard of care (LABA/ICS). Efficacy data were not collected separately for the "Salmeterol / fluticasone" and "budesonide / formoterol" Arms/Groups,"
Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. A positive change from baseline in FEV1 indicates improvement in lung function. Pulmonary function tests were performed at study visits including FEV1, and Force Vital Capacity (FVC). These were performed 30 minutes before treatment and not more than 2 hours in advance after stopping the Long-acting bronchodilators eight hours before visits. In order to reduce the variation between each test, the same instrument was used in the whole research process if condition allowed.
Outcome measures
| Measure |
Indacaterol
n=22 Participants
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium
n=154 Participants
LAMA: Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS
n=702 Participants
Salmeterol / fluticasone Or budesonide / formoterol
|
Indacaterol + Tiotropium
n=6 Participants
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS + Tiotropium
n=404 Participants
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
n=104 Participants
Oral theophylline
|
LABA/ICS + Tiotropium
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
Oral theophylline
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
|
-0.042 Liters
Standard Deviation 0.1742
|
0.006 Liters
Standard Deviation 0.2537
|
0.033 Liters
Standard Deviation 0.3790
|
0.022 Liters
Standard Deviation 0.1157
|
0.011 Liters
Standard Deviation 0.2417
|
0.012 Liters
Standard Deviation 0.3405
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline,12 monthsPopulation: FAS: Two Arms/Groups were grouped together in the analysis as some of the analysis required to combine the results. Per protocol it was not the intent to compare the results between different standard of care (LABA/ICS). Efficacy data were not collected separately for the "Salmeterol / fluticasone" and "budesonide / formoterol" Arms/Groups,"
Forced expiratory volume in 1 second (FEV1) is the amount of air that can be exhaled in one second. A positive change from baseline in FEV1 indicates improvement in lung function. Pulmonary function tests were performed at study visits including FEV1, and Force Vital Capacity (FVC). These were performed 30 minutes before treatment and not more than 2 hours in advance after stopping the long-acting bronchodilators eight hours before visits. In order to reduce the variation between each test, the same instrument was used in the whole research process if condition allowed.
Outcome measures
| Measure |
Indacaterol
n=10 Participants
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium
n=129 Participants
LAMA: Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS
n=597 Participants
Salmeterol / fluticasone Or budesonide / formoterol
|
Indacaterol + Tiotropium
n=3 Participants
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS + Tiotropium
n=317 Participants
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
n=87 Participants
Oral theophylline
|
LABA/ICS + Tiotropium
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
Oral theophylline
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
|
0.056 Liters
Standard Deviation 0.2137
|
-0.036 Liters
Standard Deviation 0.2395
|
0.056 Liters
Standard Deviation 0.4335
|
0.030 Liters
Standard Deviation 0.0854
|
-0.028 Liters
Standard Deviation 0.2258
|
0.046 Liters
Standard Deviation 0.3654
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline,12 monthsPopulation: FAS: Two Arms/Groups were grouped together in the analysis as some of the analysis required to combine the results. Per protocol it was not the intent to compare the results between different standard of care (LABA/ICS)
Number of COPD exacerbations evaluated over 12 months. COPD exacerbation is defined as a new onset or worsening of at least 1 respiratory major symptoms (e.g. dyspnea, cough, sputum volume or sputum purulence) for at least 3 consecutive days, which results in recorded treatment change (antibiotics/steroids/oxygen therapy) OR recorded COPD related hospitalization/Emergency visit. COPD exacerbation is not considered as adverse event, and should only be recorded in COPD e-CRF.
Outcome measures
| Measure |
Indacaterol
n=32 Participants
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium
n=276 Participants
LAMA: Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS
n=813 Participants
Salmeterol / fluticasone Or budesonide / formoterol
|
Indacaterol + Tiotropium
n=283 Participants
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS + Tiotropium
n=1096 Participants
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
n=9 Participants
Oral theophylline
|
LABA/ICS + Tiotropium
n=632 Participants
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
n=154 Participants
Oral theophylline
|
|---|---|---|---|---|---|---|---|---|
|
COPD Exacerbation
|
1.1 COPD Exacerbations/year
Standard Deviation 3.53
|
0.5 COPD Exacerbations/year
Standard Deviation 1.89
|
1.1 COPD Exacerbations/year
Standard Deviation 7.74
|
0.4 COPD Exacerbations/year
Standard Deviation 1.89
|
0.9 COPD Exacerbations/year
Standard Deviation 6.72
|
4.1 COPD Exacerbations/year
Standard Deviation 5.46
|
0.8 COPD Exacerbations/year
Standard Deviation 3.47
|
1.0 COPD Exacerbations/year
Standard Deviation 3.57
|
SECONDARY outcome
Timeframe: Baseline,3,6,9,12 monthsPopulation: FAS: Two Arms/Groups were grouped together in the analysis as some of the analysis required to combine the results. Per protocol it was not the intent to compare the results between different standard of care (LABA/ICS).Efficacy data were not collected separately for the "Salmeterol / fluticasone" and "budesonide / formoterol" Arms/Groups,"
The mMRC scale is scored from 0 (less severe) to 4 (severe). 0 Not troubled with breathlessness except with strenuous exercise; 1 Troubled by shortness of breath when hurrying on the level or walking up a slight hill; 2 Walks slower than people of the same age on the level because of breathlessness or has to stop for breath when walking at own pace on the level; 3 Stops for breath after walking about 100 yards or after a few minutes on the level; 4 Too breathless to leave the house or breathless when dressing or undressing. The modified Medical Research Council (mMRC) Dyspnea Scale , is a five-item instrument (part of the Borg scale) to assess a patient's degree of breathlessness in relation to physical activity. Participants will be required to read a brief description of an activity and then select a statement that best describes their experience with dyspnea at Visit 101. The mMRC was assessed by the investigators at the scheduled visits.
Outcome measures
| Measure |
Indacaterol
n=32 Participants
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium
n=276 Participants
LAMA: Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS
n=1096 Participants
Salmeterol / fluticasone Or budesonide / formoterol
|
Indacaterol + Tiotropium
n=9 Participants
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS + Tiotropium
n=632 Participants
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
n=154 Participants
Oral theophylline
|
LABA/ICS + Tiotropium
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
Oral theophylline
|
|---|---|---|---|---|---|---|---|---|
|
Change in Health Status Questionnaire MMRC
Baseline scale item 3
|
3 Number of participants
|
36 Number of participants
|
154 Number of participants
|
3 Number of participants
|
110 Number of participants
|
19 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
Baseline scale item 4
|
0 Number of participants
|
3 Number of participants
|
19 Number of participants
|
0 Number of participants
|
22 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
3 month Scale item 0
|
3 Number of participants
|
24 Number of participants
|
101 Number of participants
|
0 Number of participants
|
54 Number of participants
|
20 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
3 month Scale item 1
|
9 Number of participants
|
69 Number of participants
|
364 Number of participants
|
4 Number of participants
|
157 Number of participants
|
52 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
3 month Scale item 2
|
7 Number of participants
|
54 Number of participants
|
203 Number of participants
|
3 Number of participants
|
133 Number of participants
|
26 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
3 month Scale item 3
|
1 Number of participants
|
18 Number of participants
|
67 Number of participants
|
0 Number of participants
|
58 Number of participants
|
11 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
3 month Scale item 4
|
0 Number of participants
|
2 Number of participants
|
6 Number of participants
|
0 Number of participants
|
9 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
6 month Scale item 0
|
2 Number of participants
|
23 Number of participants
|
96 Number of participants
|
0 Number of participants
|
37 Number of participants
|
15 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
6 month Scale item 1
|
5 Number of participants
|
57 Number of participants
|
290 Number of participants
|
1 Number of participants
|
149 Number of participants
|
43 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
6 month Scale item 2
|
8 Number of participants
|
45 Number of participants
|
138 Number of participants
|
4 Number of participants
|
105 Number of participants
|
20 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
6 month Scale item 3
|
1 Number of participants
|
13 Number of participants
|
54 Number of participants
|
1 Number of participants
|
44 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
6 month Scale item 4
|
0 Number of participants
|
3 Number of participants
|
5 Number of participants
|
0 Number of participants
|
11 Number of participants
|
0 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
9 month Scale item 0
|
3 Number of participants
|
24 Number of participants
|
116 Number of participants
|
0 Number of participants
|
45 Number of participants
|
20 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
9 month Scale item 1
|
5 Number of participants
|
52 Number of participants
|
256 Number of participants
|
1 Number of participants
|
127 Number of participants
|
40 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
9 month Scale item 2
|
4 Number of participants
|
30 Number of participants
|
131 Number of participants
|
2 Number of participants
|
99 Number of participants
|
19 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
9 month Scale item 3
|
1 Number of participants
|
14 Number of participants
|
42 Number of participants
|
0 Number of participants
|
41 Number of participants
|
5 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
9 month Scale item 4
|
0 Number of participants
|
1 Number of participants
|
4 Number of participants
|
0 Number of participants
|
9 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
12 month Scale item 0
|
1 Number of participants
|
24 Number of participants
|
150 Number of participants
|
0 Number of participants
|
47 Number of participants
|
20 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
12 month Scale item 1
|
5 Number of participants
|
61 Number of participants
|
275 Number of participants
|
2 Number of participants
|
138 Number of participants
|
52 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
12 month Scale item 2
|
2 Number of participants
|
33 Number of participants
|
127 Number of participants
|
1 Number of participants
|
102 Number of participants
|
12 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
12 month Scale item 3
|
2 Number of participants
|
10 Number of participants
|
41 Number of participants
|
0 Number of participants
|
32 Number of participants
|
4 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
12 month Scale item 4
|
0 Number of participants
|
3 Number of participants
|
9 Number of participants
|
0 Number of participants
|
9 Number of participants
|
1 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
Baseline scale item 0
|
4 Number of participants
|
40 Number of participants
|
161 Number of participants
|
1 Number of participants
|
63 Number of participants
|
31 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
Baseline scale item 1
|
11 Number of participants
|
114 Number of participants
|
435 Number of participants
|
4 Number of participants
|
226 Number of participants
|
66 Number of participants
|
—
|
—
|
|
Change in Health Status Questionnaire MMRC
Baseline scale item 2
|
14 Number of participants
|
83 Number of participants
|
327 Number of participants
|
1 Number of participants
|
211 Number of participants
|
34 Number of participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline,3,6,9,12 monthsPopulation: FAS: Two Arms/Groups were grouped together in the analysis as some of the analysis required to combine the results. Per protocol it was not the intent to compare the results between different standard of care (LABA/ICS). Efficacy data were not collected separately for the "Salmeterol / fluticasone" and "budesonide / formoterol" Arms/Groups,"
The COPD assessment test (CAT) is a short instrument scale used to quantify the symptom burden of COPD and will be used to assess the health status of patients in this study. It consists of eight items, each presented as a semantic 6-point differential scale, providing a total score out of 40. A higher score indicates a worse health status. Scores of 0 - 10, 11 - 20, 21 - 30 and 31 - 40 represent a mild, moderate, severe or very severe clinical impact of COPD upon the patient.
Outcome measures
| Measure |
Indacaterol
n=32 Participants
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium
n=276 Participants
LAMA: Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS
n=1096 Participants
Salmeterol / fluticasone Or budesonide / formoterol
|
Indacaterol + Tiotropium
n=9 Participants
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS + Tiotropium
n=632 Participants
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
n=154 Participants
Oral theophylline
|
LABA/ICS + Tiotropium
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
Oral theophylline
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline in Questionnaire COPD Assessment Test (CAT) Score
9 Month
|
-4.4 Score on a scale
Standard Deviation 5.27
|
-3.1 Score on a scale
Standard Deviation 6.02
|
-3.5 Score on a scale
Standard Deviation 6.66
|
-9.0 Score on a scale
Standard Deviation 2.65
|
-3.1 Score on a scale
Standard Deviation 6.49
|
-3.1 Score on a scale
Standard Deviation 6.27
|
—
|
—
|
|
Change From Baseline in Questionnaire COPD Assessment Test (CAT) Score
3 Month
|
-1.9 Score on a scale
Standard Deviation 5.12
|
-2.1 Score on a scale
Standard Deviation 5.58
|
-2.3 Score on a scale
Standard Deviation 5.68
|
-1.9 Score on a scale
Standard Deviation 2.67
|
-1.8 Score on a scale
Standard Deviation 5.96
|
-1.8 Score on a scale
Standard Deviation 4.07
|
—
|
—
|
|
Change From Baseline in Questionnaire COPD Assessment Test (CAT) Score
6 Month
|
-1.9 Score on a scale
Standard Deviation 5.80
|
-2.7 Score on a scale
Standard Deviation 5.78
|
-2.7 Score on a scale
Standard Deviation 5.89
|
-2.7 Score on a scale
Standard Deviation 5.01
|
-2.2 Score on a scale
Standard Deviation 6.46
|
-2.5 Score on a scale
Standard Deviation 5.65
|
—
|
—
|
|
Change From Baseline in Questionnaire COPD Assessment Test (CAT) Score
12 Month
|
-5.1 Score on a scale
Standard Deviation 3.98
|
-2.6 Score on a scale
Standard Deviation 6.74
|
-4.1 Score on a scale
Standard Deviation 7.09
|
-7.7 Score on a scale
Standard Deviation 0.58
|
-3.7 Score on a scale
Standard Deviation 6.45
|
-2.4 Score on a scale
Standard Deviation 7.25
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline,3,6,9,12 monthsPopulation: FAS: Two Arms/Groups were grouped together in the analysis as some of the analysis required to combine the results. Per protocol it was not the intent to compare the results between different standard of care (LABA/ICS). Efficacy data were not collected separately for the "Salmeterol / fluticasone" and "budesonide / formoterol" Arms/Groups,"
Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. BDI/TDI was used to assess dyspnea from several aspects, caused by daily activities. These were evaluated by the investigators in the study at the scheduled study visits. The indices were to be evaluated by the same investigator.as far as possible.
Outcome measures
| Measure |
Indacaterol
n=32 Participants
LABA: Indacaterol, once a day, 150μg each time
|
Tiotropium
n=276 Participants
LAMA: Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS
n=1096 Participants
Salmeterol / fluticasone Or budesonide / formoterol
|
Indacaterol + Tiotropium
n=9 Participants
Indacaterol, once a day, 150μg each time +Tiotropium Bromide, once a day, 18 μg
|
LABA/ICS + Tiotropium
n=632 Participants
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
n=154 Participants
Oral theophylline
|
LABA/ICS + Tiotropium
(Salmeterol / fluticasone Or budesonide / formoterol) + tiotropium
|
Oral Theophylline
Oral theophylline
|
|---|---|---|---|---|---|---|---|---|
|
Change From Baseline Questionnaire Transition Dyspnea Index (TDI) Score
3 Month
|
1.4 Units on a scale
Standard Deviation 2.61
|
1.2 Units on a scale
Standard Deviation 2.43
|
1.3 Units on a scale
Standard Deviation 2.59
|
0.4 Units on a scale
Standard Deviation 2.07
|
1.1 Units on a scale
Standard Deviation 2.50
|
0.9 Units on a scale
Standard Deviation 2.57
|
—
|
—
|
|
Change From Baseline Questionnaire Transition Dyspnea Index (TDI) Score
Baseline
|
6.7 Units on a scale
Standard Deviation 2.27
|
6.6 Units on a scale
Standard Deviation 2.66
|
6.7 Units on a scale
Standard Deviation 2.66
|
5.4 Units on a scale
Standard Deviation 2.24
|
6.2 Units on a scale
Standard Deviation 2.60
|
7.1 Units on a scale
Standard Deviation 2.81
|
—
|
—
|
|
Change From Baseline Questionnaire Transition Dyspnea Index (TDI) Score
6 Month
|
0.0 Units on a scale
Standard Deviation 2.45
|
1.0 Units on a scale
Standard Deviation 2.67
|
1.4 Units on a scale
Standard Deviation 2.59
|
-0.5 Units on a scale
Standard Deviation 2.26
|
0.9 Units on a scale
Standard Deviation 2.36
|
1.2 Units on a scale
Standard Deviation 2.03
|
—
|
—
|
|
Change From Baseline Questionnaire Transition Dyspnea Index (TDI) Score
9 Month
|
0.7 Units on a scale
Standard Deviation 1.23
|
0.9 Units on a scale
Standard Deviation 2.48
|
1.6 Units on a scale
Standard Deviation 2.78
|
1.0 Units on a scale
Standard Deviation 1.73
|
0.9 Units on a scale
Standard Deviation 2.32
|
1.4 Units on a scale
Standard Deviation 2.68
|
—
|
—
|
|
Change From Baseline Questionnaire Transition Dyspnea Index (TDI) Score
12 Month
|
0.3 Units on a scale
Standard Deviation 1.70
|
1.0 Units on a scale
Standard Deviation 2.91
|
1.7 Units on a scale
Standard Deviation 3.09
|
1.0 Units on a scale
Standard Deviation 1.73
|
1.0 Units on a scale
Standard Deviation 2.57
|
1.6 Units on a scale
Standard Deviation 2.44
|
—
|
—
|
Adverse Events
Indacaterol
Tiotropium
Salemeterol/Fluticasone
Budesonide/Formoterol
Indacaterol + Tiotropium
Salemeterol/Fluticasone(or Budesonide/Formoterol)+Tiotropium
Oral Theophylline
Other
Serious adverse events
| Measure |
Indacaterol
n=32 participants at risk
Indacaterol
|
Tiotropium
n=276 participants at risk
Tiotropium
|
Salemeterol/Fluticasone
n=813 participants at risk
Salemeterol/Fluticasone
|
Budesonide/Formoterol
n=283 participants at risk
Budesonide/Formoterol
|
Indacaterol + Tiotropium
n=9 participants at risk
Indacaterol + Tiotropium
|
Salemeterol/Fluticasone(or Budesonide/Formoterol)+Tiotropium
n=632 participants at risk
Salemeterol/Fluticasone(or Budesonide/Formoterol)+Tiotropium
|
Oral Theophylline
n=154 participants at risk
Oral Theophylline
|
Other
n=30 participants at risk
Other
|
|---|---|---|---|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Brain neoplasm
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant lung neoplasm
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.16%
1/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.35%
1/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Cardiac disorders
Acute coronary syndrome
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Cardiac disorders
Acute left ventricular failure
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.65%
1/154
|
0.00%
0/30
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/32
|
0.00%
0/276
|
0.25%
2/813
|
0.00%
0/283
|
0.00%
0/9
|
0.32%
2/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Cardiac disorders
Atrioventricular block
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Cardiac disorders
Cardiac disorder
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
11.1%
1/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.65%
1/154
|
0.00%
0/30
|
|
Cardiac disorders
Hypertensive heart disease
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Cardiac disorders
Palpitations
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.16%
1/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Cardiac disorders
Unstable angina
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.16%
1/632
|
0.65%
1/154
|
0.00%
0/30
|
|
Cardiac disorders
Ventricular arrhythmia
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Ear and labyrinth disorders
Positional vertigo
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Endocrine disorders
Goitre
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
3.3%
1/30
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.65%
1/154
|
0.00%
0/30
|
|
Gastrointestinal disorders
Inguinal hernia
|
3.1%
1/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.35%
1/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/32
|
0.36%
1/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
General disorders
Death
|
0.00%
0/32
|
0.36%
1/276
|
0.25%
2/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
General disorders
Multi-organ failure
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
General disorders
Sudden cardiac death
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.65%
1/154
|
0.00%
0/30
|
|
General disorders
Sudden death
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.32%
2/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Abdominal infection
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Appendicitis
|
0.00%
0/32
|
0.36%
1/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Bronchitis
|
0.00%
0/32
|
0.36%
1/276
|
0.37%
3/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/32
|
0.36%
1/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Infectious pneumonia
|
0.00%
0/32
|
0.72%
2/276
|
0.00%
0/813
|
0.00%
0/283
|
11.1%
1/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Lower respiratory tract infection
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Lung infection
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.16%
1/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.16%
1/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Injury, poisoning and procedural complications
Hip fracture
|
0.00%
0/32
|
0.36%
1/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/32
|
0.36%
1/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Musculoskeletal and connective tissue disorders
Rheumatoid arthritis
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.16%
1/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Musculoskeletal and connective tissue disorders
Spondyloarthropathy
|
0.00%
0/32
|
0.36%
1/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
0.00%
0/9
|
0.16%
1/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Nervous system disorders
Post herpetic neuralgia
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Reproductive system and breast disorders
Benign prostatic hyperplasia
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Bronchiectasis
|
0.00%
0/32
|
0.00%
0/276
|
0.12%
1/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/32
|
0.00%
0/276
|
0.25%
2/813
|
0.00%
0/283
|
0.00%
0/9
|
0.00%
0/632
|
1.3%
2/154
|
0.00%
0/30
|
|
Respiratory, thoracic and mediastinal disorders
Spontaneous pneumothorax
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.35%
1/283
|
0.00%
0/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
|
Vascular disorders
Hypertension
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
11.1%
1/9
|
0.00%
0/632
|
0.00%
0/154
|
0.00%
0/30
|
Other adverse events
| Measure |
Indacaterol
n=32 participants at risk
Indacaterol
|
Tiotropium
n=276 participants at risk
Tiotropium
|
Salemeterol/Fluticasone
n=813 participants at risk
Salemeterol/Fluticasone
|
Budesonide/Formoterol
n=283 participants at risk
Budesonide/Formoterol
|
Indacaterol + Tiotropium
n=9 participants at risk
Indacaterol + Tiotropium
|
Salemeterol/Fluticasone(or Budesonide/Formoterol)+Tiotropium
n=632 participants at risk
Salemeterol/Fluticasone(or Budesonide/Formoterol)+Tiotropium
|
Oral Theophylline
n=154 participants at risk
Oral Theophylline
|
Other
n=30 participants at risk
Other
|
|---|---|---|---|---|---|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
6.2%
2/32
|
0.36%
1/276
|
1.7%
14/813
|
0.35%
1/283
|
0.00%
0/9
|
0.63%
4/632
|
0.65%
1/154
|
3.3%
1/30
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/32
|
0.00%
0/276
|
0.00%
0/813
|
0.00%
0/283
|
11.1%
1/9
|
0.16%
1/632
|
0.00%
0/154
|
0.00%
0/30
|
Additional Information
Study Director
Novartis Pharmaceutical
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER