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Trial record 99 of 183 for:    Foradil Combi OR symbicort OR (Budesonide AND formeterol)

Efficacy and Tolerability Study in Severe Chronic Obstructive Pulmonary Disease (COPD) Patients (SECURE2)

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ClinicalTrials.gov Identifier: NCT01415518
Recruitment Status : Completed
First Posted : August 12, 2011
Results First Posted : August 26, 2014
Last Update Posted : July 9, 2019
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Chronic Obstructive Pulmonary Disease (COPD)
Interventions Drug: Drug: Budesonide/formoterol (Symbicort Turbuhaler
Drug: Drug: ipratropium (AtroventTM)
Drug: theophylline SR
Enrollment 581
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description 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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Period Title: Overall Study
Started 292 292
Patients Who Received Study Treatment 290 292
Pts With Correct Randomized Treatment 290 [1] 289 [2]
Completed 276 261
Not Completed 16 31
Reason Not Completed
Withdrawal by Subject             2             12
Protocol Violation             6             8
Lost to Follow-up             3             5
Adverse Event             3             4
Death             1             1
Condition under Investigation Worsened             1             1
[1]
Efficacy analysis used 290 patients. Safety analysis used 290+3=293 patients.
[2]
Efficacy analysis used 292 patients. Safety analysis used 292-3=289 patients.
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR Total
Hide Arm/Group Description 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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily) Total of all reporting groups
Overall Number of Baseline Participants 290 292 582
Hide Baseline Analysis Population Description
Two patients in 'Symbicort Turbuhaler + ipratropium + theophylline' group did not receive study treatment and were excluded from the analysis popolation. Thus the number of patients in that group is 290 (= 290 - 2).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 290 participants 292 participants 582 participants
63.8  (8.79) 64.4  (8.76) 64.1  (8.77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 290 participants 292 participants 582 participants
Female
36
  12.4%
43
  14.7%
79
  13.6%
Male
254
  87.6%
249
  85.3%
503
  86.4%
1.Primary Outcome
Title Pre-dose FEV1
Hide Description Ratio of pre-dose FEV1 (Forced Expiratory Volume in 1 second) in treatment period to baseline value
Time Frame Baseline (week 0) and mean in treatment period (weeks 1, 6, 12) measured before inhalation of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 286 286
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.079
(1.059 to 1.100)
1.009
(0.990 to 1.029)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.069
Confidence Interval (2-Sided) 95%
1.043 to 1.096
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Post-dose FEV1 at 5 Minutes
Hide Description Ratio of post-dose FEV1 at 5 minutes to baseline value
Time Frame Baseline (-2 weeks) and mean in treatment period (1, 6, 12 weeks) measured at 5 minutes after inhalation of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 288 292
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.179
(1.161 to 1.199)
1.106
(1.088 to 1.124)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.067
Confidence Interval (2-Sided) 95%
1.044 to 1.090
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Post-dose FEV1 at 60 Minutes
Hide Description Ratio of post-dose FEV1 at 60 minutes to baseline value
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 288 292
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.219
(1.199 to 1.240)
1.142
(1.123 to 1.162)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.068
Confidence Interval 95%
1.043 to 1.092
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Pre-dose FVC
Hide Description Ratio of pre-dose FVC (Forced Vital Capacity) to baseline
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 286 286
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.072
(1.054 to 1.090)
1.030
(1.013 to 1.048)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.040
Confidence Interval (2-Sided) 95%
1.017 to 1.064
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Post-dose FVC at 5 Minutes
Hide Description Ratio of post-dose FVC at 5 minutes to baseline
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 288 292
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.170
(1.153 to 1.188)
1.120
(1.104 to 1.137)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.045
Confidence Interval (2-Sided) 95%
1.024 to 1.065
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Post-dose FVC at 60 Minutes
Hide Description Ratio of post-dose FVC at 60 minutes to baseline
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 288 292
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.192
(1.174 to 1.211)
1.148
(1.130 to 1.166)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.038
Confidence Interval (2-Sided) 95%
1.017 to 1.060
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Pre-dose IC
Hide Description Ratio of pre-dose IC (Inspiratory Capacity) to baseline
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 276 264
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.068
(1.045 to 1.092)
1.032
(1.010 to 1.056)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0248
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.035
Confidence Interval (2-Sided) 95%
1.004 to 1.066
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Post-dose IC at 60 Minutes
Hide Description Ratio of post-dose IC at 60 minutes to baseline
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 278 271
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratio
1.163
(1.140 to 1.187)
1.120
(1.097 to 1.143)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0074
Comments [Not Specified]
Method ANCOVA
Comments Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.038
Confidence Interval (2-Sided) 95%
1.010 to 1.067
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Pre-dose PEF in Last Week of Treatment
Hide Description Change in pre-dose morning PEF (Peak Expiratory Flow) from run-in period to last week of treatment
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 207 191
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
23.135
(13.808 to 32.462)
-2.038
(-11.678 to 7.603)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 25.172
Confidence Interval (2-Sided) 95%
12.733 to 37.611
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Pre-dose PEF in First Week of Treatment
Hide Description Change in pre-dose morning PEF from run-in period to first week of treatment
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 228 215
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
24.393
(16.799 to 31.987)
3.257
(-4.357 to 10.871)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 21.136
Confidence Interval (2-Sided) 95%
12.163 to 30.110
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Pre-dose PEF in Whole Treatment Period
Hide Description Change in pre-dose morning PEF from run-in period to whole treatment period
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 247 246
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
21.021
(14.563 to 27.479)
-2.023
(-8.555 to 4.510)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 23.044
Confidence Interval (2-Sided) 95%
14.927 to 31.161
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Post-dose PEF in Last Week of Treatment
Hide Description Change in post-dose morning PEF at 5 minutes from run-period to last week of treatment
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 158 156
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
36.612
(26.656 to 46.569)
5.100
(-4.702 to 14.901)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 31.513
Confidence Interval (2-Sided) 95%
18.740 to 44.286
Estimation Comments [Not Specified]
13.Secondary Outcome
Title Post-dose PEF in First Week of Treatment
Hide Description Change in post-dose morning PEF at 5 minutes from run-in period to first week of treatment
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 170 179
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
25.993
(17.330 to 34.656)
1.670
(-6.582 to 9.922)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 24.322
Confidence Interval (2-Sided) 95%
14.425 to 34.220
Estimation Comments [Not Specified]
14.Secondary Outcome
Title Post-dose PEF in Whole Treatment Period
Hide Description Change in post-dose morning PEF at 5 minutes from run-period to whole treatment period
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 237 239
Least Squares Mean (95% Confidence Interval)
Unit of Measure: L/min
26.507
(19.892 to 33.122)
-0.662
(-7.278 to 5.955)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 27.168
Confidence Interval (2-Sided) 95%
18.906 to 35.431
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Use of Reliever Medication During Day in the Last Week on Treatment
Hide Description Change in the number of inhalations of reliever medication during day from run-in to the last week on treatment
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 273 266
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.398
(-0.570 to -0.226)
-0.101
(-0.276 to 0.074)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0102
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.297
Confidence Interval (2-Sided) 95%
-0.522 to -0.071
Estimation Comments [Not Specified]
16.Secondary Outcome
Title Use of Reliever Medication During Day in the First Week on Treatment
Hide Description Change in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 283 282
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.440
(-0.583 to -0.297)
-0.097
(-0.241 to 0.047)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0004
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.343
Confidence Interval (2-Sided) 95%
-0.533 to -0.153
Estimation Comments [Not Specified]
17.Secondary Outcome
Title Use of Reliever Medication During Day in the Whole Treatment Period
Hide Description Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 283 285
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.404
(-0.539 to -0.268)
-0.061
(-0.197 to 0.075)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.342
Confidence Interval (2-Sided) 95%
-0.523 to -0.162
Estimation Comments [Not Specified]
18.Secondary Outcome
Title Change in COPD Symptoms - Breathing
Hide Description Change in breathing symptom score (from 0 (none) to 4 (severe)) from run-in period
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 284 287
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score from 0 to 4
-0.507
(-0.584 to -0.431)
-0.229
(-0.305 to -0.152)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of score as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.279
Confidence Interval (2-Sided) 95%
-0.381 to -0.177
Estimation Comments [Not Specified]
19.Secondary Outcome
Title COPD Symptoms - Cough
Hide Description Change in cough symptom score (from 0 (none) to 4 (almost constant)) from run-in period
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 284 287
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score from 0 to 4
-0.441
(-0.516 to -0.365)
-0.248
(-0.324 to -0.172)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of score as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.193
Confidence Interval (2-Sided) 95%
-0.294 to -0.092
Estimation Comments [Not Specified]
20.Secondary Outcome
Title COPD Symptoms Sputum
Hide Description Change in sputum symptom score (from 0 (none) to 4 (severe)) from run-in period
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 284 287
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Score from 0 to 4
-0.332
(-0.407 to -0.257)
-0.124
(-0.200 to -0.049)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0001
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of score as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.208
Confidence Interval (2-Sided) 95%
-0.308 to -0.108
Estimation Comments [Not Specified]
21.Secondary Outcome
Title COPD Exacerbations
Hide Description Severe exacerbations requiring systemic steroids (oral ≥3 days or parenteral) or hospitalisation or emergency room treatment due to worsening of COPD symptoms
Time Frame Whole treatment period (12 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 290 292
Least Squares Mean (95% Confidence Interval)
Unit of Measure: exacerbations/12 weeks
0.069
(0.044 to 0.106)
0.121
(0.087 to 0.170)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0425
Comments [Not Specified]
Method Poisson regression
Comments Poisson regression model with treatment as a factor and the duration time in study as an offset variable
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.565
Confidence Interval (2-Sided) 95%
0.325 to 0.981
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0880
Comments [Not Specified]
Method Regression, Cox
Comments Time to the first COPD exacerbation
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.604
Confidence Interval (2-Sided) 95%
0.339 to 1.078
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0845
Comments [Not Specified]
Method Log Rank
Comments Time to the first COPD exacerbation
22.Secondary Outcome
Title Use of Reliever Medication During Night in the Last Week on Treatment
Hide Description Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 269 263
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.078
(-0.147 to -0.009)
-0.023
(-0.093 to 0.046)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2281
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.055
Confidence Interval (2-Sided) 95%
-0.144 to 0.035
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Use of Reliever Medication During Night in the First Week on Treatment
Hide Description change in the number of inhalations of reliever medication during day from run-in to the first week on treatment
Time Frame 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 treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 278 282
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.124
(-0.179 to -0.068)
-0.002
(-0.057 to 0.053)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.122
Confidence Interval (2-Sided) 95%
-0.194 to -0.049
Estimation Comments [Not Specified]
24.Secondary Outcome
Title Use of Reliever Medication During Night in the Whole Treatment Period
Hide Description Change in the number of inhalations of reliever medication during day from run-in to the whole treatment period
Time Frame 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)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description:
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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
Overall Number of Participants Analyzed 280 284
Least Squares Mean (95% Confidence Interval)
Unit of Measure: times/day
-0.086
(-0.144 to -0.027)
0.020
(-0.038 to 0.079)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Symbicort Turbuhaler + Ipratropium + Theophylline SR, Ipratropium + Theophylline SR
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0073
Comments [Not Specified]
Method ANCOVA
Comments Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.106
Confidence Interval (2-Sided) 95%
-0.183 to -0.029
Estimation Comments [Not Specified]
Time Frame 3 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Hide Arm/Group Description 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 (AtroventTM 20 μg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)
All-Cause Mortality
Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Affected / at Risk (%) Affected / at Risk (%)
Total   9/293 (3.07%)   10/289 (3.46%) 
Cardiac disorders     
Coronary artery disease *  1/293 (0.34%)  0/289 (0.00%) 
Gastrointestinal disorders     
Fungal oesophagitis *  1/293 (0.34%)  0/289 (0.00%) 
Gastritis atrophic *  1/293 (0.34%)  0/289 (0.00%) 
Hepatobiliary disorders     
Hepatic cirrhosis *  0/293 (0.00%)  1/289 (0.35%) 
Infections and infestations     
Tuberculosis *  1/293 (0.34%)  0/289 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture *  0/293 (0.00%)  1/289 (0.35%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease *  7/293 (2.39%)  7/289 (2.42%) 
Asphyxia *  0/293 (0.00%)  1/289 (0.35%) 
Lung infection *  1/293 (0.34%)  0/289 (0.00%) 
Organising pneumonia *  1/293 (0.34%)  0/289 (0.00%) 
Pneumonia *  1/293 (0.34%)  0/289 (0.00%) 
Skin and subcutaneous tissue disorders     
Erysipelas *  1/293 (0.34%)  0/289 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Symbicort Turbuhaler + Ipratropium + Theophylline SR Ipratropium + Theophylline SR
Affected / at Risk (%) Affected / at Risk (%)
Total   33/293 (11.26%)   31/289 (10.73%) 
Cardiac disorders     
Palpitations *  1/293 (0.34%)  1/289 (0.35%) 
Coronary artery disease *  1/293 (0.34%)  0/289 (0.00%) 
Gastrointestinal disorders     
Diarrhoea *  1/293 (0.34%)  1/289 (0.35%) 
Abdominal pain *  1/293 (0.34%)  0/289 (0.00%) 
Fungal oesophagitis *  1/293 (0.34%)  0/289 (0.00%) 
Gastritis atrophic *  1/293 (0.34%)  0/289 (0.00%) 
Periodontitis *  1/293 (0.34%)  0/289 (0.00%) 
Toothache *  0/293 (0.00%)  1/289 (0.35%) 
General disorders     
Pyrexia *  3/293 (1.02%)  3/289 (1.04%) 
Chest discomfort *  0/293 (0.00%)  1/289 (0.35%) 
Asthenia *  0/293 (0.00%)  1/289 (0.35%) 
Hepatobiliary disorders     
Cholecystitis acute *  0/293 (0.00%)  1/289 (0.35%) 
Hepatic cirrhosis *  0/293 (0.00%)  1/289 (0.35%) 
Immune system disorders     
Hypersensitivity *  1/293 (0.34%)  0/289 (0.00%) 
Infections and infestations     
Tuberculosis *  1/293 (0.34%)  0/289 (0.00%) 
Injury, poisoning and procedural complications     
Femoral neck fracture *  0/293 (0.00%)  1/289 (0.35%) 
Joint sprain *  1/293 (0.34%)  0/289 (0.00%) 
Nervous system disorders     
Dizziness *  1/293 (0.34%)  1/289 (0.35%) 
Headache *  0/293 (0.00%)  1/289 (0.35%) 
Tremor *  0/293 (0.00%)  1/289 (0.35%) 
Psychiatric disorders     
Insomnia *  1/293 (0.34%)  0/289 (0.00%) 
Sleep disorder *  0/293 (0.00%)  1/289 (0.35%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease *  7/293 (2.39%)  7/289 (2.42%) 
Nasopharyngitis *  4/293 (1.37%)  6/289 (2.08%) 
Upper respiratory tract infection *  4/293 (1.37%)  2/289 (0.69%) 
Cough *  1/293 (0.34%)  3/289 (1.04%) 
Haemoptysis *  2/293 (0.68%)  0/289 (0.00%) 
Productive cough *  1/293 (0.34%)  1/289 (0.35%) 
Chest discomfort *  0/293 (0.00%)  1/289 (0.35%) 
Asphyxia *  0/293 (0.00%)  1/289 (0.35%) 
Lung infection *  1/293 (0.34%)  0/289 (0.00%) 
Organising pneumonia *  1/293 (0.34%)  0/289 (0.00%) 
Oropharyngeal pain *  1/293 (0.34%)  0/289 (0.00%) 
Pharyngitis *  1/293 (0.34%)  0/289 (0.00%) 
Pneumonia *  1/293 (0.34%)  0/289 (0.00%) 
Sputum increased *  0/293 (0.00%)  1/289 (0.35%) 
Tachypnoea *  0/293 (0.00%)  1/289 (0.35%) 
Skin and subcutaneous tissue disorders     
Erysipelas *  1/293 (0.34%)  0/289 (0.00%) 
Erythema of eyelid *  0/293 (0.00%)  1/289 (0.35%) 
Vascular disorders     
Hypertension *  1/293 (0.34%)  0/289 (0.00%) 
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Goran Eckerwall
Organization: AstraZeneca
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01415518     History of Changes
Other Study ID Numbers: D589BL00022
First Submitted: August 8, 2011
First Posted: August 12, 2011
Results First Submitted: November 25, 2013
Results First Posted: August 26, 2014
Last Update Posted: July 9, 2019