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CompletedNCT01415518SECURE2Updated Jul 9, 2019Results posted

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

A Phase 4 interventional study of Drug: Budesonide/formoterol (Symbicort Turbuhaler and Drug: ipratropium (AtroventTM) in Chronic Obstructive Pulmonary Disease (COPD), sponsored by AstraZeneca. Completed at 21 sites in China. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2019-07-09.

Sponsored by AstraZeneca · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
581
Allocation
Randomized
Ages
40 Years and older
Sex
All
01

Study summary

Efficacy and tolerability study in severe chronic obstructive pulmonary disease (COPD) patients.

Read the detailed description

Efficacy and tolerability study of Symbicort Turbuhaler (160/4.5µg/inhalation,2inhalations twice daily) added to Atrovent (20µg/inhalation, 2 inhalations 4 times daily) + theophylline SR(0.1g/tablet, 1 tablet p.o. twice daily) compared with Atrovent + theophylline SR in severe COPD patients.

02

Conditions studied

  • Chronic Obstructive Pulmonary Disease (COPD)

Keywords

  • Severe chronic obstructive pulmonary disease (COPD) patients
03

In context

Lung Diseases

3,303 studies on the registry are indexed under Lung Diseases; 355 are open to participants now.

This study's enrollment of 581 is above the median of 72 across 2,118 interventional studies indexed under Lung Diseases.

Browse Lung Diseases studies →

Lead sponsor

AstraZeneca is the lead sponsor of 3,429 studies on the registry; 270 are open to participants now.

Of its 357 completed or terminated interventional studies of FDA-regulated products, 173 (48%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Signed and dated informed consent
  • Men or women patients ≥ 40 years of age
  • Diagnosis of COPD with symptoms for more than 2 years and there is a history of at least one COPD exacerbation requiring a course of oral steroids and/or antibiotics within 1-12 months before Visit 2
  • Forced Expiratory Volume in 1 second (FEV1) ≤50% of predicted normal value, pre-bronchodilator and Forced Expiratory Volume in 1 second (FEV1) / Forced Vital Capacity (FVC) \< 70%, pre-bronchodilator
  • Total symptom score of 2 or more per day for at least half of run-in period (breathing, cough and sputum scores from the diary card) and complete morning recordings of Digital Peak Flow Meter data at least 7 out of the last 10 days of the run-in period

Exclusion criteria

Exclusion Criteria:

  • A history of asthma and seasonal allergic rhinitis before 40 years of age
  • Patients who have experienced exacerbation of COPD requiring hospitalisation and /or emergency room treatment and/or a course of oral steroids and/or intravenous corticosteroids and/or antibiotics within 4 weeks prior to Visit 2 and/or during run-in period
  • Patients with relevant cardiovascular disorder judged by the investigator
  • Patients with glaucoma, prostatic hyperplasia or bladder-neck obstruction judged by the investigator
  • Women who are pregnant, breast-feeding or of child-bearing potential judged by the investigator
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
581 participants (actual)

Study arms

  • Other
    1

    budesonide/formoterol (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)

    Drug: Drug: Budesonide/formoterol (Symbicort Turbuhaler · Drug: Drug: ipratropium (AtroventTM) · Drug: theophylline SR

  • Other
    2

    ipratropium (AtroventTM 20 µg/inhalation, 2 inhalations four times daily) + theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)

    Drug: Drug: ipratropium (AtroventTM) · Drug: theophylline SR

Interventions

  • DrugDrug: Budesonide/formoterol (Symbicort Turbuhaler

    budesonide/formoterol (Symbicort Turbuhaler 160/4.5µg/inhalation, 2 inhalations twice daily)

  • DrugDrug: ipratropium (AtroventTM)

    ipratropium (AtroventTM 20 µg/inhalation, 2 inhalations four times daily)

  • Drugtheophylline SR

    theophylline SR (0.1g/tablet, 1 tablet p.o. twice daily)

06

What researchers measure

Primary outcomes

  1. Pre-dose FEV1

    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

Secondary outcomes

  1. Post-dose FEV1 at 5 Minutes

    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

  2. Post-dose FEV1 at 60 Minutes

    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)

  3. Pre-dose FVC

    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)

  4. Post-dose FVC at 5 Minutes

    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)

  5. Post-dose FVC at 60 Minutes

    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)

  6. Pre-dose IC

    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)

  7. Post-dose IC at 60 Minutes

    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)

  8. Pre-dose PEF in Last Week of Treatment

    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

  9. Pre-dose PEF in First Week of Treatment

    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

  10. Pre-dose PEF in Whole Treatment Period

    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)

  11. Post-dose PEF in Last Week of Treatment

    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

  12. Post-dose PEF in First Week of Treatment

    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

  13. Post-dose PEF in Whole Treatment Period

    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)

  14. Use of Reliever Medication During Day in the Last Week on Treatment

    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

  15. Use of Reliever Medication During Day in the First Week on Treatment

    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

  16. Use of Reliever Medication During Day in the Whole Treatment Period

    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)

  17. Change in COPD Symptoms - Breathing

    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)

  18. COPD Symptoms - Cough

    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)

  19. COPD Symptoms Sputum

    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)

  20. COPD Exacerbations

    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)

  21. Use of Reliever Medication During Night in the Last Week on Treatment

    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

  22. Use of Reliever Medication During Night in the First Week on Treatment

    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

  23. Use of Reliever Medication During Night in the Whole Treatment Period

    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)

07

Results

Posted Aug 26, 2014

Participant flow

Participant flow — Overall Study
MilestoneSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Started292292
Patients who received study treatment290292
Pts with correct randomized treatment290289
Completed276261
Not completed1631
Withdrew: Withdrawal by subject212
Withdrew: Protocol violation68
Withdrew: Lost to follow-up35
Withdrew: Adverse event34
Withdrew: Death11
Withdrew: Condition under investigation worsened11

Outcome measures

PrimaryPre-dose FEV1

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
Reported as:
Geometric mean · Ratio
Pre-dose FEV1
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Pre-dose FEV11.079 (1.059 to 1.100)1.009 (0.990 to 1.029)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Ratio: 1.069 · 95% CI 1.043 to 1.096multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPost-dose FEV1 at 5 Minutes

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
Reported as:
Geometric mean · Ratio
Post-dose FEV1 at 5 Minutes
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose FEV1 at 5 Minutes1.179 (1.161 to 1.199)1.106 (1.088 to 1.124)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Ratio: 1.067 · 95% CI 1.044 to 1.090Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPost-dose FEV1 at 60 Minutes

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)
Reported as:
Geometric mean · Ratio
Post-dose FEV1 at 60 Minutes
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose FEV1 at 60 Minutes1.219 (1.199 to 1.240)1.142 (1.123 to 1.162)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Ratio: 1.068 · 95% CI 1.043 to 1.092Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPre-dose FVC

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)
Reported as:
Geometric mean · Ratio
Pre-dose FVC
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Pre-dose FVC1.072 (1.054 to 1.090)1.030 (1.013 to 1.048)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0007 · Ratio: 1.040 · 95% CI 1.017 to 1.064Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPost-dose FVC at 5 Minutes

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)
Reported as:
Geometric mean · Ratio
Post-dose FVC at 5 Minutes
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose FVC at 5 Minutes1.170 (1.153 to 1.188)1.120 (1.104 to 1.137)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Ratio: 1.045 · 95% CI 1.024 to 1.065Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPost-dose FVC at 60 Minutes

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)
Reported as:
Geometric mean · Ratio
Post-dose FVC at 60 Minutes
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose FVC at 60 Minutes1.192 (1.174 to 1.211)1.148 (1.130 to 1.166)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0003 · Ratio: 1.038 · 95% CI 1.017 to 1.060Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPre-dose IC

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)
Reported as:
Geometric mean · Ratio
Pre-dose IC
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Pre-dose IC1.068 (1.045 to 1.092)1.032 (1.010 to 1.056)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0248 · Ratio: 1.035 · 95% CI 1.004 to 1.066Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPost-dose IC at 60 Minutes

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)
Reported as:
Geometric mean · Ratio
Post-dose IC at 60 Minutes
RatioSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose IC at 60 Minutes1.163 (1.140 to 1.187)1.120 (1.097 to 1.143)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0074 · Ratio: 1.038 · 95% CI 1.010 to 1.067Multiplicative ANCOVA model with treatment and centre as fixed factors and baseline value as a (log-transformed) covariate
SecondaryPre-dose PEF in Last Week of Treatment

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
Reported as:
Least squares mean · L/min
Pre-dose PEF in Last Week of Treatment
L/minSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Pre-dose PEF in Last Week of Treatment23.135 (13.808 to 32.462)-2.038 (-11.678 to 7.603)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0001 · Mean difference (net): 25.172 · 95% CI 12.733 to 37.611Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
SecondaryPre-dose PEF in First Week of Treatment

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
Reported as:
Least squares mean · L/min
Pre-dose PEF in First Week of Treatment
L/minSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Pre-dose PEF in First Week of Treatment24.393 (16.799 to 31.987)3.257 (-4.357 to 10.871)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Mean difference (net): 21.136 · 95% CI 12.163 to 30.110Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
SecondaryPre-dose PEF in Whole Treatment Period

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)
Reported as:
Least squares mean · L/min
Pre-dose PEF in Whole Treatment Period
L/minSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Pre-dose PEF in Whole Treatment Period21.021 (14.563 to 27.479)-2.023 (-8.555 to 4.510)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Mean difference (net): 23.044 · 95% CI 14.927 to 31.161Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
SecondaryPost-dose PEF in Last Week of Treatment

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
Reported as:
Least squares mean · L/min
Post-dose PEF in Last Week of Treatment
L/minSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose PEF in Last Week of Treatment36.612 (26.656 to 46.569)5.100 (-4.702 to 14.901)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Mean difference (net): 31.513 · 95% CI 18.740 to 44.286Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
SecondaryPost-dose PEF in First Week of Treatment

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
Reported as:
Least squares mean · L/min
Post-dose PEF in First Week of Treatment
L/minSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose PEF in First Week of Treatment25.993 (17.330 to 34.656)1.670 (-6.582 to 9.922)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Mean difference (net): 24.322 · 95% CI 14.425 to 34.220Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
SecondaryPost-dose PEF in Whole Treatment Period

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)
Reported as:
Least squares mean · L/min
Post-dose PEF in Whole Treatment Period
L/minSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Post-dose PEF in Whole Treatment Period26.507 (19.892 to 33.122)-0.662 (-7.278 to 5.955)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Mean difference (net): 27.168 · 95% CI 18.906 to 35.431Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of pre-dose morning PEF as a covariate
SecondaryUse of Reliever Medication During Day in the Last Week on Treatment

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
Reported as:
Least squares mean · times/day
Use of Reliever Medication During Day in the Last Week on Treatment
times/daySymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Use of Reliever Medication During Day in the Last Week on Treatment-0.398 (-0.570 to -0.226)-0.101 (-0.276 to 0.074)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0102 · Mean difference (net): -0.297 · 95% CI -0.522 to -0.071Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
SecondaryUse of Reliever Medication During Day in the First Week on Treatment

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
Reported as:
Least squares mean · times/day
Use of Reliever Medication During Day in the First Week on Treatment
times/daySymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Use of Reliever Medication During Day in the First Week on Treatment-0.440 (-0.583 to -0.297)-0.097 (-0.241 to 0.047)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0004 · Mean difference (net): -0.343 · 95% CI -0.533 to -0.153Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
SecondaryUse of Reliever Medication During Day in the Whole Treatment Period

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)
Reported as:
Least squares mean · times/day
Use of Reliever Medication During Day in the Whole Treatment Period
times/daySymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Use of Reliever Medication During Day in the Whole Treatment Period-0.404 (-0.539 to -0.268)-0.061 (-0.197 to 0.075)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0002 · Mean difference (net): -0.342 · 95% CI -0.523 to -0.162Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
SecondaryChange in COPD Symptoms - Breathing

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)
Reported as:
Least squares mean · Score from 0 to 4
Change in COPD Symptoms - Breathing
Score from 0 to 4Symbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Change in COPD Symptoms - Breathing-0.507 (-0.584 to -0.431)-0.229 (-0.305 to -0.152)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = <.0001 · Mean difference (net): -0.279 · 95% CI -0.381 to -0.177Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of score as a covariate
SecondaryCOPD Symptoms - Cough

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)
Reported as:
Least squares mean · Score from 0 to 4
COPD Symptoms - Cough
Score from 0 to 4Symbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
COPD Symptoms - Cough-0.441 (-0.516 to -0.365)-0.248 (-0.324 to -0.172)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0002 · Mean difference (net): -0.193 · 95% CI -0.294 to -0.092Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of score as a covariate
SecondaryCOPD Symptoms Sputum

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)
Reported as:
Least squares mean · Score from 0 to 4
COPD Symptoms Sputum
Score from 0 to 4Symbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
COPD Symptoms Sputum-0.332 (-0.407 to -0.257)-0.124 (-0.200 to -0.049)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0001 · Mean difference (net): -0.208 · 95% CI -0.308 to -0.108Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of score as a covariate
SecondaryCOPD Exacerbations

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)
Reported as:
Least squares mean · exacerbations/12 weeks
COPD Exacerbations
exacerbations/12 weeksSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
COPD Exacerbations0.069 (0.044 to 0.106)0.121 (0.087 to 0.170)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · Poisson regression · p = 0.0425 · Rate ratio: 0.565 · 95% CI 0.325 to 0.981Poisson regression model with treatment as a factor and the duration time in study as an offset variable
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · Regression, Cox · p = 0.0880 · Hazard ratio (hr): 0.604 · 95% CI 0.339 to 1.078Time to the first COPD exacerbation
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · Log Rank · p = 0.0845Time to the first COPD exacerbation
SecondaryUse of Reliever Medication During Night in the Last Week on Treatment

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
Reported as:
Least squares mean · times/day
Use of Reliever Medication During Night in the Last Week on Treatment
times/daySymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Use of Reliever Medication During Night in the Last Week on Treatment-0.078 (-0.147 to -0.009)-0.023 (-0.093 to 0.046)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.2281 · Mean difference (net): -0.055 · 95% CI -0.144 to 0.035Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
SecondaryUse of Reliever Medication During Night in the First Week on Treatment

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
Reported as:
Least squares mean · times/day
Use of Reliever Medication During Night in the First Week on Treatment
times/daySymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Use of Reliever Medication During Night in the First Week on Treatment-0.124 (-0.179 to -0.068)-0.002 (-0.057 to 0.053)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0010 · Mean difference (net): -0.122 · 95% CI -0.194 to -0.049Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate
SecondaryUse of Reliever Medication During Night in the Whole Treatment Period

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)
Reported as:
Least squares mean · times/day
Use of Reliever Medication During Night in the Whole Treatment Period
times/daySymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Use of Reliever Medication During Night in the Whole Treatment Period-0.086 (-0.144 to -0.027)0.020 (-0.038 to 0.079)
Statistical analysis
  • Symbicort Turbuhaler + Ipratropium + Theophylline SR vs Ipratropium + Theophylline SR · ANCOVA · p = 0.0073 · Mean difference (net): -0.106 · 95% CI -0.183 to -0.029Additive ANCOVA model with treatment and centre as fixed factors and the run-in mean of reliever medication as a covariate

Adverse events

Collected over 3 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Symbicort Turbuhaler + Ipratropium + Theophylline SR—9/293 (3.1%)33/293 (11.3%)
Ipratropium + Theophylline SR—10/289 (3.5%)31/289 (10.7%)
Most frequent serious events
Showing 10 of 12
Most frequent serious events
EventSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders7/2937/289
AsphyxiaRespiratory, thoracic and mediastinal disorders0/2931/289
Hepatic cirrhosisHepatobiliary disorders0/2931/289
Femoral neck fractureInjury, poisoning and procedural complications0/2931/289
Lung infectionRespiratory, thoracic and mediastinal disorders1/2930/289
Organising pneumoniaRespiratory, thoracic and mediastinal disorders1/2930/289
PneumoniaRespiratory, thoracic and mediastinal disorders1/2930/289
Coronary artery diseaseCardiac disorders1/2930/289
Fungal oesophagitisGastrointestinal disorders1/2930/289
Gastritis atrophicGastrointestinal disorders1/2930/289
Most frequent other events
Showing 10 of 40
Most frequent other events
EventSymbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SR
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders7/2937/289
NasopharyngitisRespiratory, thoracic and mediastinal disorders4/2936/289
Upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders4/2932/289
CoughRespiratory, thoracic and mediastinal disorders1/2933/289
PyrexiaGeneral disorders3/2933/289
HaemoptysisRespiratory, thoracic and mediastinal disorders2/2930/289
Productive coughRespiratory, thoracic and mediastinal disorders1/2931/289
DiarrhoeaGastrointestinal disorders1/2931/289
DizzinessNervous system disorders1/2931/289
PalpitationsCardiac disorders1/2931/289

Baseline characteristics

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
Age, Continuous(years)Symbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SRTotal
Mean63.8 ± 8.7964.4 ± 8.7664.1 ± 8.77
Sex: Female, Male
Sex: Female, Male(Participants)Symbicort Turbuhaler + Ipratropium + Theophylline SRIpratropium + Theophylline SRTotal
Female364379
Male254249503
08

Study locations

21 sites
  • Research Site
    Beijing, Beijing, China
  • Research Site
    Foshan, Guangdong, China
  • Research Site
    Guangzhou, Guangdong, China
  • Research Site
    Zhongshan, Guangdong, China
  • Research Site
    Haikou, Hainan, China
  • Research Site
    Shijiazhuang, Hebei, China
  • Research Site
    Tangshan, Hebei, China
  • Research Site
    Zhengzhou, Henan, China
  • Research Site
    Wuhan, Hubei, China
  • Research Site
    Changsha, Hunan, China
  • Research Site
    Nanjing, Jiangsu, China
  • Research Site
    Changchun, Jilin, China
  • Research Site
    Shenyang, Liaoning, China
  • Research Site
    Qingdao, Shandong, China
  • Research Site
    Shanghai, Shanghai, China
  • Research Site
    Tianjin, Tianjin, China
  • Research Site
    Chengdu, China
  • Research Site
    Chongqin, China
  • Research Site
    Da Lian, China
  • Research Site
    Ha'er BING, China
  • Research Site
    Huhehaote, China
09

References and documents

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 9, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01415518
Lead sponsor
AstraZeneca
Responsible party
Sponsor
First posted
Aug 12, 2011
Start date
Sep 1, 2011
Primary completion
Dec 1, 2012
Completion
Dec 1, 2012
Results posted
Aug 26, 2014
Last update
Jul 9, 2019

Study contacts

Samuel Chen
study chair · AstraZeneca Singapore Pte Ltd
View the source record on ClinicalTrials.gov ↗

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