Trial Outcomes & Findings for Efficacy and Tolerability Study in Severe Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT01415518)
NCT ID: NCT01415518
Last Updated: 2019-07-09
Results Overview
Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
581 participants
Primary outcome timeframe
Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
Results posted on
2019-07-09
Participant Flow
Participant milestones
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Overall Study
STARTED
|
292
|
292
|
|
Overall Study
Patients Who Received Study Treatment
|
290
|
292
|
|
Overall Study
Pts With Correct Randomized Treatment
|
290
|
289
|
|
Overall Study
COMPLETED
|
276
|
261
|
|
Overall Study
NOT COMPLETED
|
16
|
31
|
Reasons for withdrawal
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
2
|
12
|
|
Overall Study
Protocol Violation
|
6
|
8
|
|
Overall Study
Lost to Follow-up
|
3
|
5
|
|
Overall Study
Adverse Event
|
3
|
4
|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
Condition under Investigation Worsened
|
1
|
1
|
Baseline Characteristics
Efficacy and Tolerability Study in Severe Chronic Obstructive Pulmonary Disease (COPD) Patients
Baseline characteristics by cohort
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=290 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=292 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Total
n=582 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.8 years
STANDARD_DEVIATION 8.79 • n=5 Participants
|
64.4 years
STANDARD_DEVIATION 8.76 • n=7 Participants
|
64.1 years
STANDARD_DEVIATION 8.77 • n=5 Participants
|
|
Sex: Female, Male
Female
|
36 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
79 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
254 Participants
n=5 Participants
|
249 Participants
n=7 Participants
|
503 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drugPopulation: FAS
Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=286 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=286 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Pre-dose FEV1
|
1.079 Ratio
Interval 1.059 to 1.1
|
1.009 Ratio
Interval 0.99 to 1.029
|
SECONDARY outcome
Timeframe: Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drugPopulation: FAS
Ratio of post-dose FEV1 at 5 minutes to baseline value
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=288 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=292 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose FEV1 at 5 Minutes
|
1.179 Ratio
Interval 1.161 to 1.199
|
1.106 Ratio
Interval 1.088 to 1.124
|
SECONDARY outcome
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)Population: FAS
Ratio of post-dose FEV1 at 60 minutes to baseline value
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=288 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=292 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose FEV1 at 60 Minutes
|
1.219 Ratio
Interval 1.199 to 1.24
|
1.142 Ratio
Interval 1.123 to 1.162
|
SECONDARY outcome
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)Ratio of pre-dose FVC (Forced Vital Capacity) to baseline
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=286 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=286 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Pre-dose FVC
|
1.072 Ratio
Interval 1.054 to 1.09
|
1.030 Ratio
Interval 1.013 to 1.048
|
SECONDARY outcome
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 5 minutes after inhalation of study drug at weeks 0, 1, 6, 12)Ratio of post-dose FVC at 5 minutes to baseline
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=288 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=292 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose FVC at 5 Minutes
|
1.170 Ratio
Interval 1.153 to 1.188
|
1.120 Ratio
Interval 1.104 to 1.137
|
SECONDARY outcome
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)Ratio of post-dose FVC at 60 minutes to baseline
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=288 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=292 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose FVC at 60 Minutes
|
1.192 Ratio
Interval 1.174 to 1.211
|
1.148 Ratio
Interval 1.13 to 1.166
|
SECONDARY outcome
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)Ratio of pre-dose IC (Inspiratory Capacity) to baseline
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=276 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=264 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Pre-dose IC
|
1.068 Ratio
Interval 1.045 to 1.092
|
1.032 Ratio
Interval 1.01 to 1.056
|
SECONDARY outcome
Timeframe: Baseline (meaured before inhalation of study drug at week 0) and mean in treatment period (measured at 1 hour after inhalation of study drug at weeks 0, 1, 6, 12)Ratio of post-dose IC at 60 minutes to baseline
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=278 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=271 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose IC at 60 Minutes
|
1.163 Ratio
Interval 1.14 to 1.187
|
1.120 Ratio
Interval 1.097 to 1.143
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in the last week of treatmentChange in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=207 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=191 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Pre-dose PEF in Last Week of Treatment
|
23.135 L/min
Interval 13.808 to 32.462
|
-2.038 L/min
Interval -11.678 to 7.603
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured before inhalation of study drug in the first week of treatmentChange in pre-dose morning PEF from run-in period to first week of treatment
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=228 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=215 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Pre-dose PEF in First Week of Treatment
|
24.393 L/min
Interval 16.799 to 31.987
|
3.257 L/min
Interval -4.357 to 10.871
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured before inhalation of study drug in whole treatment period (12 weeks)Change in pre-dose morning PEF from run-in period to whole treatment period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=247 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=246 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Pre-dose PEF in Whole Treatment Period
|
21.021 L/min
Interval 14.563 to 27.479
|
-2.023 L/min
Interval -8.555 to 4.51
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in the last week of treatmentChange in post-dose morning PEF at 5 minutes from run-period to last week of treatment
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=158 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=156 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose PEF in Last Week of Treatment
|
36.612 L/min
Interval 26.656 to 46.569
|
5.100 L/min
Interval -4.702 to 14.901
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurments measured at 5 minutes after inhalation of study drug in the first week of treatmentChange in post-dose morning PEF at 5 minutes from run-in period to first week of treatment
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=170 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=179 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose PEF in First Week of Treatment
|
25.993 L/min
Interval 17.33 to 34.656
|
1.670 L/min
Interval -6.582 to 9.922
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured at 5 minutes after inhalation of study drug in whole treatment period (12 weeks)Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=237 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=239 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Post-dose PEF in Whole Treatment Period
|
26.507 L/min
Interval 19.892 to 33.122
|
-0.662 L/min
Interval -7.278 to 5.955
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the last week on treatmentChange in the number of inhalations of reliever medication during day from run-in to the last week on treatment
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=273 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=266 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Use of Reliever Medication During Day in the Last Week on Treatment
|
-0.398 times/day
Interval -0.57 to -0.226
|
-0.101 times/day
Interval -0.276 to 0.074
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the first week on treatmentChange in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=283 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=282 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Use of Reliever Medication During Day in the First Week on Treatment
|
-0.440 times/day
Interval -0.583 to -0.297
|
-0.097 times/day
Interval -0.241 to 0.047
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during day in the whole treatment period (12 weeks)Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=283 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=285 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Use of Reliever Medication During Day in the Whole Treatment Period
|
-0.404 times/day
Interval -0.539 to -0.268
|
-0.061 times/day
Interval -0.197 to 0.075
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)Change in breathing symptom score (from 0 (none) to 4 (severe)) from run-in period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=284 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=287 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Change in COPD Symptoms - Breathing
|
-0.507 Score from 0 to 4
Interval -0.584 to -0.431
|
-0.229 Score from 0 to 4
Interval -0.305 to -0.152
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)Change in cough symptom score (from 0 (none) to 4 (almost constant)) from run-in period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=284 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=287 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
COPD Symptoms - Cough
|
-0.441 Score from 0 to 4
Interval -0.516 to -0.365
|
-0.248 Score from 0 to 4
Interval -0.324 to -0.172
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements in the whole treatment period (12 weeks)Change in sputum symptom score (from 0 (none) to 4 (severe)) from run-in period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=284 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=287 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
COPD Symptoms Sputum
|
-0.332 Score from 0 to 4
Interval -0.407 to -0.257
|
-0.124 Score from 0 to 4
Interval -0.2 to -0.049
|
SECONDARY outcome
Timeframe: Whole treatment period (12 weeks)Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=290 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=292 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
COPD Exacerbations
|
0.069 exacerbations/12 weeks
Interval 0.044 to 0.106
|
0.121 exacerbations/12 weeks
Interval 0.087 to 0.17
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the last week on treatmentChange in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=269 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=263 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Use of Reliever Medication During Night in the Last Week on Treatment
|
-0.078 times/day
Interval -0.147 to -0.009
|
-0.023 times/day
Interval -0.093 to 0.046
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the first week on treatmentchange in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=278 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=282 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Use of Reliever Medication During Night in the First Week on Treatment
|
-0.124 times/day
Interval -0.179 to -0.068
|
-0.002 times/day
Interval -0.057 to 0.053
|
SECONDARY outcome
Timeframe: Mean of daily measurements in run-in period (the last 10 days before randomization) and mean of daily measurements measured during night in the whole treatment period (12 weeks)Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Outcome measures
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=280 Participants
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=284 Participants
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Use of Reliever Medication During Night in the Whole Treatment Period
|
-0.086 times/day
Interval -0.144 to -0.027
|
0.020 times/day
Interval -0.038 to 0.079
|
Adverse Events
Symbicort Turbuhaler + Ipratropium + Theophylline SR
Serious events: 9 serious events
Other events: 33 other events
Deaths: 0 deaths
Ipratropium + Theophylline SR
Serious events: 10 serious events
Other events: 31 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=293 participants at risk
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=289 participants at risk
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.4%
7/293 • 3 months
|
2.4%
7/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Asphyxia
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Cardiac disorders
Coronary artery disease
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Gastrointestinal disorders
Fungal oesophagitis
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Gastrointestinal disorders
Gastritis atrophic
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Infections and infestations
Tuberculosis
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Skin and subcutaneous tissue disorders
Erysipelas
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
Other adverse events
| Measure |
Symbicort Turbuhaler + Ipratropium + Theophylline SR
n=293 participants at risk
Symbicort Turbuhaler 160/4.5μg/inhalation, 2 inhalations twice daily) added to ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
Ipratropium + Theophylline SR
n=289 participants at risk
ipratropium (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.4%
7/293 • 3 months
|
2.4%
7/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasopharyngitis
|
1.4%
4/293 • 3 months
|
2.1%
6/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
1.4%
4/293 • 3 months
|
0.69%
2/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.34%
1/293 • 3 months
|
1.0%
3/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.68%
2/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.34%
1/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
General disorders
Pyrexia
|
1.0%
3/293 • 3 months
|
1.0%
3/289 • 3 months
|
|
Gastrointestinal disorders
Diarrhoea
|
0.34%
1/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Nervous system disorders
Dizziness
|
0.34%
1/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Cardiac disorders
Palpitations
|
0.34%
1/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Cardiac disorders
Coronary artery disease
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Gastrointestinal disorders
Abdominal pain
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Gastrointestinal disorders
Fungal oesophagitis
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Gastrointestinal disorders
Gastritis atrophic
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Gastrointestinal disorders
Periodontitis
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Nervous system disorders
Headache
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Nervous system disorders
Tremor
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Chest discomfort
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Asphyxia
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngitis
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Sputum increased
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
General disorders
Chest discomfort
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
General disorders
Asthenia
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Injury, poisoning and procedural complications
Joint sprain
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Psychiatric disorders
Insomnia
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Skin and subcutaneous tissue disorders
Erysipelas
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Skin and subcutaneous tissue disorders
Erythema of eyelid
|
0.00%
0/293 • 3 months
|
0.35%
1/289 • 3 months
|
|
Immune system disorders
Hypersensitivity
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Infections and infestations
Tuberculosis
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
|
Vascular disorders
Hypertension
|
0.34%
1/293 • 3 months
|
0.00%
0/289 • 3 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee PI shall not publish any results until the earlier of (i) the date of the first Study results publication authorized by AZ and (ii) the end of the 18 month period following the completion of the Study. PI shall provide AZ with such material for review, at least 60 days prior to submission for publication. If requested in writing by AZ, PI shall withhold material from submission for publication for an additional 90 days from the date of AZ's request.
- Publication restrictions are in place
Restriction type: OTHER