Pulmonary Disease, Chronic Obstructive
Conditions
Brief summary
This is a randomised study to be conducted in patients with severe to very severe Chronic Obstructive Pulmonary Disease (COPD) to establish whether there is a need for these patients to be continuously treated with an inhaled corticosteroid on top of two potent long-acting bronchodilators. The study also aims to identify the type of patients who are likely to benefit from inhaled corticosteroid maintenance therapy.
Interventions
DRUGtiotropium inhalation
DRUGfluticasone propionate
DRUGplacebo matched for fluticasone propionate
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 40 years or more 2. Severe to very severe chronic obstructive pulmonary disease (COPD) 3. Current or ex-smoker with smoking history of at least 10 pack years 4. At least one documented exacerbation of COPD in previous year
Exclusion criteria
1. Significant diseases other than COPD; significant alcohol or drug abuse 2. Current clinical diagnosis of asthma requiring steroid treatment 3. History of thoracotomy with pulmonary resection 4. Regular use of daytime oxygen 5. Recent history (within 3 months) of myocardial infarction 6. Recent (within 6 weeks) respiratory infection or COPD exacerbation 7. Recent (within 6 weeks) treatment with systemic corticosteroids at doses in excess of 5milligram / day 8. Recent (within 3 months) unstable or life-threatening cardiac arrhythmia requiring intervention 9. Recent (within 1 year) hospitalisation for cardiac failure 10. Malignancy requiring chemotherapy or radiotherapy 11. Clinical diagnosis of bronchiectasis 12. Pregnant or nursing women 13. Known hypersensitivity to study drugs 14. Current or recent (within 30 days) participation in another clinical study 15. Current participation in or recent completion (within 4 weeks) of a pulmonary rehabilitation program
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Moderate or Severe On-treatment COPD Exacerbation | During randomised treatment, up to 488 days | A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as an increase or new onset of ≥2 lower respiratory symptoms related to COPD, with ≥1 symptom lasting ≥3 days, requiring a change in treatment. Lower respiratory symptoms included shortness of breath, sputum production (volume), sputum purulence, cough, wheezing and chest tightness. A change in treatment included: hospitalisation/treatment in an urgent care unit, prescription of antibiotics and/or systemic steroids or a significant change of prescribed respiratory medication such as theophyllines, long-acting beta-agonists or inhaled corticosteroids. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.The measure type displays the 25th percentile and its 95% confidence interval. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation | During randomised treatment, up to 488 days | Presence (yes vs no) of at least one moderate or severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids. |
| Time to First Severe On-treatment COPD Exacerbation | During randomised treatment, up to 488 days | Time to first severe on-treatment COPD exacerbation. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. The measure type displays the 25th percentile and its 95% confidence interval. |
| Number of Severe On-treatment COPD Exacerbations | During randomised treatment, up to 488 days | Number of severe on-treatment COPD exacerbations based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined and counted as severe if ≥1 of the contributing exacerbation events was severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Measured values show adjusted event rate. |
| Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation. | During randomised treatment, up to 488 days | Presence (yes vs no) of at least one severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. |
| Time to First On-treatment COPD Exacerbation | During randomised treatment, up to 488 days | Time to first on-treatment COPD exacerbation of any severity. The measure type displays the 25th percentile and its 95% confidence interval. |
| Number of On-treatment COPD Exacerbations | During randomised treatment, up to 488 days | Number of on-treatment COPD exacerbations of any severity, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined. Measured values show adjusted event rate. |
| Proportion of Patients With at Least One On-treatment COPD Exacerbation | During randomised treatment, up to 488 days | Presence (yes vs no) of at least one on-treatment COPD exacerbation of any severity, displayed as a percentage. |
| Severity of On-treatment COPD Exacerbations | During randomised treatment, up to 488 days | Severity of on-treatment COPD exacerbations: for each patient, the worst applicable category was taken (i.e. none, mild, moderate or severe) |
| Change in On-treatment Lung Function as Measured by Trough FEV1 | Baseline and week 6, 12, 18 and 52 visits | Change from baseline in on-treatment lung function as measured by trough forced expiratory volume in one second (FEV1); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale | Baseline and week 18 and 52 visits | Change from baseline in on-treatment dyspnoea as measured by the Modified Medical Research Council (MMRC) dyspnoea scale; change was calculated as week score minus baseline score. Negative changes from baseline indicate an improvement in health. Scale from 0 to 4: * 0 = not troubled by breathlessness, except during strenuous exercise * 1 = short of breath when hurrying or walking up a slight hill * 2 = walks slower than contemporaries on the same level because of breathlessness, or has to stop for breath when walking at own pace * 3 = stops for breath after approximately 100 yards, or after a few minutes on the level * 4 = too breathless to leave the house, or breathless when dressing or undressing No breathlessness was given a score of -1 Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain | Baseline and week 27 and 52 visits | Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Impact Domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI) | Baseline and week 18 and 52 visits | Change from baseline in on-treatment physical health status as determined by body mass index (BMI); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Number of Moderate or Severe On-treatment COPD Exacerbations | During randomised treatment, up to 488 days | Number of moderate or severe on-treatment COPD exacerbations, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined and counted as moderate or severe if ≥1 of the contributing exacerbation events was moderate or severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids. Measured values show adjusted mean event rate. |
| Change in On-treatment BODE Index | Baseline and week 18 and 52 visits | Change from baseline in on-treatment BODE index (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity index), a composite score ranging from 0 (best) to 10 (worst); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain | Baseline and week 12, 18 and 52 visits | Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to extremely/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to cough. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain | Baseline and week 27 and 52 visits | Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Symptoms domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain | Baseline and week 12, 18 and 52 visits | Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to a lot/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to cough. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain | Baseline and week 12, 18 and 52 visits | Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to a lot/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to sputum. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain | Baseline and week 12, 18 and 52 visits | Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to extremely/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to sputum. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment FEV1 as Measured by Home Based Spirometry | Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits | Change from baseline in on-treatment Forced Expiratory Volume in One Second (FEV1) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if ≥4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment FVC as Measured by Home Based Spirometry | Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits | Change from baseline in on-treatment forced vital capacity (FVC) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if ≥4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment PEFR as Measured by Home Based Spirometry | Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits | Change from baseline in on-treatment peak expiratory flow rate (PEFR) as measured by home based spirometry; change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain | Baseline and week 27 and 52 visits | Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Activity domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score | Baseline and week 27 and 52 visits | Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Total score. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment Physician Global Evaluation | Baseline and week 27 and 52 visits | Change from baseline in on-treatment physician global evaluation. The evaluation reflected the physician's opinion of the patient's overall condition and was based on the need for concomitant medication, the number and severity of exacerbations, the severity of cough, the ability to exercise, the amount of wheezing and any other relevant clinical observations. Patients were graded on a scale of 1 (poor) to 8 (excellent). Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
| Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT) | Baseline and week 18 and 52 visits | Change from baseline in on-treatment exercise capacity measured by six-minute walk test (6-MWT); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest. |
Countries
Australia, Belgium, Brazil, Bulgaria, China, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, New Zealand, Philippines, Poland, Russia, South Africa, Spain, Taiwan, Tunisia, Turkey (Türkiye), Ukraine, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fluticasone Maintenance 18μg tiotropium administered by oral inhalation once daily (q.d.), 50μg salmeterol and 500μg fluticasone, each administered by oral inhalation twice daily (b.i.d) for 6 weeks (open-label run in period), followed by 18 μg tiotropium q.d., 50 μg salmeterol b.i.d.,and 500 μg fluticasone b.i.d. for 52 weeks (randomised treatment period). | 1,243 |
| Fluticasone Withdrawal 18μg tiotropium administered by oral inhalation once daily (q.d.), 50μg salmeterol and 500μg fluticasone, each administered by oral inhalation twice daily (b.i.d) for 6 weeks (open-label run in period), followed by 18 μg tiotropium q.d.and 50 μg salmeterol b.i.d. for 52 weeks, in combination with a stepwise withdrawal of fluticasone, consisting of 250μg fluticasone b.i.d for 6 weeks, followed by 100μg fluticasone b.i.d for 6 weeks, followed by placebo for 40 weeks (randomised treatment period). | 1,242 |
| Total | 2,485 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 108 | 101 |
| Overall Study | Lack of Efficacy | 6 | 6 |
| Overall Study | Lost to Follow-up | 9 | 7 |
| Overall Study | Not treated | 1 | 2 |
| Overall Study | Other reason not defined above | 29 | 33 |
| Overall Study | Protocol Violation | 27 | 23 |
| Overall Study | Withdrawal by Subject | 48 | 61 |
Baseline characteristics
| Characteristic | Fluticasone Maintenance | Fluticasone Withdrawal | Total |
|---|---|---|---|
| Age, Continuous | 63.6 years STANDARD_DEVIATION 8.6 | 64.0 years STANDARD_DEVIATION 8.4 | 63.8 years STANDARD_DEVIATION 8.5 |
| Sex: Female, Male Female | 230 Participants | 206 Participants | 436 Participants |
| Sex: Female, Male Male | 1013 Participants | 1036 Participants | 2049 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 464 / 1,243 | 458 / 1,242 |
| serious Total, serious adverse events | 292 / 1,243 | 300 / 1,242 |
Outcome results
Primary
Time to First Moderate or Severe On-treatment COPD Exacerbation
A Chronic Obstructive Pulmonary Disease (COPD) exacerbation was defined as an increase or new onset of ≥2 lower respiratory symptoms related to COPD, with ≥1 symptom lasting ≥3 days, requiring a change in treatment. Lower respiratory symptoms included shortness of breath, sputum production (volume), sputum purulence, cough, wheezing and chest tightness. A change in treatment included: hospitalisation/treatment in an urgent care unit, prescription of antibiotics and/or systemic steroids or a significant change of prescribed respiratory medication such as theophyllines, long-acting beta-agonists or inhaled corticosteroids. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.The measure type displays the 25th percentile and its 95% confidence interval.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Maintenance | Time to First Moderate or Severe On-treatment COPD Exacerbation | 107.0 days |
| Fluticasone Withdrawal | Time to First Moderate or Severe On-treatment COPD Exacerbation | 110.0 days |
p-value: 0.349795% CI: [0.941, 1.189]Chi-squared
Secondary
Change in On-treatment BODE Index
Change from baseline in on-treatment BODE index (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity index), a composite score ranging from 0 (best) to 10 (worst); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 18 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment BODE Index | Week 52 visit (N=931, 907) | -0.03 units on a scale | Standard Error 0.04 |
| Fluticasone Maintenance | Change in On-treatment BODE Index | Week 18 visit (N=1038, 1024) | -0.06 units on a scale | Standard Error 0.03 |
| Fluticasone Withdrawal | Change in On-treatment BODE Index | Week 18 visit (N=1038, 1024) | 0.06 units on a scale | Standard Error 0.03 |
| Fluticasone Withdrawal | Change in On-treatment BODE Index | Week 52 visit (N=931, 907) | 0.14 units on a scale | Standard Error 0.04 |
Comparison: Week 52 visitp-value: 0.003395% CI: [0.05, 0.27]Restricted maximum likelihood
Secondary
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain
Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to extremely/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to cough. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 12, 18 and 52 visits
Population: Treated set who completed CASA-Q
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain | Week 18 visit (N=302, 312) | -2.87 units on a scale | Standard Error 1.035 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain | Week 12 visit (N=307, 319) | -1.65 units on a scale | Standard Error 0.986 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain | Week 52 visit (N=268, 269) | -4.51 units on a scale | Standard Error 1.063 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain | Week 12 visit (N=307, 319) | -1.24 units on a scale | Standard Error 0.968 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain | Week 18 visit (N=302, 312) | -3.71 units on a scale | Standard Error 1.018 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain | Week 52 visit (N=268, 269) | -5.54 units on a scale | Standard Error 1.057 |
Comparison: Week 52 visitp-value: 0.491495% CI: [-3.98, 1.91]Restricted maximum likelihood
Secondary
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain
Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Cough symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to a lot/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to cough. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 12, 18 and 52 visits
Population: Treated set who completed CASA-Q
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain | Week 18 visit (N=305, 312) | -1.47 units on a scale | Standard Error 1.103 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain | Week 12 visit (N=309, 318) | -0.32 units on a scale | Standard Error 1.062 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain | Week 52 visit (N=270, 268) | -1.69 units on a scale | Standard Error 1.18 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain | Week 18 visit (N=305, 312) | -3.34 units on a scale | Standard Error 1.091 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain | Week 12 visit (N=309, 318) | -0.85 units on a scale | Standard Error 1.048 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain | Week 52 visit (N=270, 268) | -3.26 units on a scale | Standard Error 1.18 |
Comparison: Week 52 visitp-value: 0.34995% CI: [-4.84, 1.71]Restricted maximum likelihood
Secondary
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain
Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum impact domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to a lot/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less impact due to sputum. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 12, 18 and 52 visits
Population: Treated set who completed CASA-Q
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain | Week 12 visit (N=308, 317) | -2.26 units on a scale | Standard Error 0.996 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain | Week 18 visit (N=303, 310) | -2.38 units on a scale | Standard Error 0.977 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain | Week 52 visit (N=267, 267) | -4.29 units on a scale | Standard Error 1.047 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain | Week 52 visit (N=267, 267) | -4.15 units on a scale | Standard Error 1.045 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain | Week 12 visit (N=308, 317) | -1.63 units on a scale | Standard Error 0.983 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain | Week 18 visit (N=303, 310) | -3.31 units on a scale | Standard Error 0.967 |
Comparison: Week 52 visitp-value: 0.926295% CI: [-2.77, 3.04]Restricted maximum likelihood
Secondary
Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain
Change from baseline in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only): Sputum symptoms domain. Change was calculated as week score minus baseline score. Response options for the items in this domain range from not at all/never to extremely/always on a five-point scale. Domain items were reverse scored, summed and transformed to a domain score ranging from 0 to 100 where a higher score is associated with less symptoms due to sputum. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 12, 18 and 52 visits
Population: Treated set who completed CASA-Q
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain | Week 12 visit (N=308, 317) | -1.36 units on a scale | Standard Error 1.154 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain | Week 18 visit (N=302, 311) | -2.71 units on a scale | Standard Error 1.119 |
| Fluticasone Maintenance | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain | Week 52 visit (N=269, 268) | -5.10 units on a scale | Standard Error 1.212 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain | Week 12 visit (N=308, 317) | -1.24 units on a scale | Standard Error 1.139 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain | Week 18 visit (N=302, 311) | -1.93 units on a scale | Standard Error 1.105 |
| Fluticasone Withdrawal | Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain | Week 52 visit (N=269, 268) | -2.45 units on a scale | Standard Error 1.211 |
Comparison: Week 52 visitp-value: 0.124195% CI: [-0.73, 6.01]Restricted maximum likelihood
Secondary
Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT)
Change from baseline in on-treatment exercise capacity measured by six-minute walk test (6-MWT); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 18 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT) | Week 18 visit (N=1111, 1110) | 3.89 meters | Standard Error 1.993 |
| Fluticasone Maintenance | Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT) | Week 52 visit (N=1013, 987) | 3.94 meters | Standard Error 2.231 |
| Fluticasone Withdrawal | Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT) | Week 18 visit (N=1111, 1110) | 1.94 meters | Standard Error 1.993 |
| Fluticasone Withdrawal | Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT) | Week 52 visit (N=1013, 987) | 0.42 meters | Standard Error 2.252 |
Comparison: Week 52 visitp-value: 0.266395% CI: [-9.74, 2.69]Restricted maximum likelihood
Secondary
Change in On-treatment FEV1 as Measured by Home Based Spirometry
Change from baseline in on-treatment Forced Expiratory Volume in One Second (FEV1) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if ≥4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 6 visit (N=893, 939) | -0.049 Litres | Standard Error 0.0066 |
| Fluticasone Maintenance | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 18 visit (N=913, 901) | -0.051 Litres | Standard Error 0.0068 |
| Fluticasone Maintenance | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 27 visit (N=863, 843) | -0.056 Litres | Standard Error 0.0071 |
| Fluticasone Maintenance | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 36 visit (N=854, 845) | -0.059 Litres | Standard Error 0.0074 |
| Fluticasone Maintenance | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 45 visit (N=830, 815) | -0.061 Litres | Standard Error 0.008 |
| Fluticasone Maintenance | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 52 visit (N=785, 788) | -0.067 Litres | Standard Error 0.0087 |
| Fluticasone Maintenance | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 12 visit (N=910, 930) | -0.050 Litres | Standard Error 0.0068 |
| Fluticasone Withdrawal | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 6 visit (N=893, 939) | -0.053 Litres | Standard Error 0.0065 |
| Fluticasone Withdrawal | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 12 visit (N=910, 930) | -0.056 Litres | Standard Error 0.0067 |
| Fluticasone Withdrawal | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 45 visit (N=830, 815) | -0.103 Litres | Standard Error 0.008 |
| Fluticasone Withdrawal | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 18 visit (N=913, 901) | -0.093 Litres | Standard Error 0.0068 |
| Fluticasone Withdrawal | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 27 visit (N=863, 843) | -0.092 Litres | Standard Error 0.0072 |
| Fluticasone Withdrawal | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 52 visit (N=785, 788) | -0.115 Litres | Standard Error 0.0087 |
| Fluticasone Withdrawal | Change in On-treatment FEV1 as Measured by Home Based Spirometry | Week 36 visit (N=854, 845) | -0.099 Litres | Standard Error 0.0074 |
Comparison: Week 52 visitp-value: <0.000195% CI: [-0.073, -0.024]Restricted maximum likelihood
Secondary
Change in On-treatment FVC as Measured by Home Based Spirometry
Change from baseline in on-treatment forced vital capacity (FVC) as measured by home based spirometry. Change was calculated as week score minus baseline score. The weekly mean was defined as the mean of the measurements taken during the last 7 days prior to the visit date, and was calculated if ≥4 of the 7 days had non-missing measurements. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 18 visit (N=913, 901) | -0.122 Litres | Standard Error 0.0177 |
| Fluticasone Maintenance | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 36 visit (N=854, 845) | -0.135 Litres | Standard Error 0.017 |
| Fluticasone Maintenance | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 12 visit (N=910, 930) | -0.113 Litres | Standard Error 0.0168 |
| Fluticasone Maintenance | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 45 visit (N=830, 815) | -0.141 Litres | Standard Error 0.0174 |
| Fluticasone Maintenance | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 52 visit (N=785, 788) | -0.157 Litres | Standard Error 0.018 |
| Fluticasone Maintenance | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 27 visit (N=863, 843) | -0.123 Litres | Standard Error 0.0167 |
| Fluticasone Maintenance | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 6 visit (N=893, 939) | -0.116 Litres | Standard Error 0.0179 |
| Fluticasone Withdrawal | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 45 visit (N=830, 815) | -0.168 Litres | Standard Error 0.0175 |
| Fluticasone Withdrawal | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 6 visit (N=893, 939) | -0.089 Litres | Standard Error 0.0177 |
| Fluticasone Withdrawal | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 12 visit (N=910, 930) | -0.105 Litres | Standard Error 0.0167 |
| Fluticasone Withdrawal | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 18 visit (N=913, 901) | -0.124 Litres | Standard Error 0.0177 |
| Fluticasone Withdrawal | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 27 visit (N=863, 843) | -0.147 Litres | Standard Error 0.0167 |
| Fluticasone Withdrawal | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 36 visit (N=854, 845) | -0.158 Litres | Standard Error 0.0171 |
| Fluticasone Withdrawal | Change in On-treatment FVC as Measured by Home Based Spirometry | Week 52 visit (N=785, 788) | -0.201 Litres | Standard Error 0.018 |
Comparison: Week 52 visitp-value: 0.085595% CI: [-0.094, 0.006]Restricted maximum likelihood
Secondary
Change in On-treatment Lung Function as Measured by Trough FEV1
Change from baseline in on-treatment lung function as measured by trough forced expiratory volume in one second (FEV1); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 6, 12, 18 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 6 visit (N=1135, 1135) | -0.009 Litres | Standard Error 0.0062 |
| Fluticasone Maintenance | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 12 visit (N=1114, 1092) | -0.011 Litres | Standard Error 0.0062 |
| Fluticasone Maintenance | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 18 visit (N=1077, 1058) | -0.011 Litres | Standard Error 0.0064 |
| Fluticasone Maintenance | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 52 visit (N=970, 935) | -0.016 Litres | Standard Error 0.0094 |
| Fluticasone Withdrawal | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 52 visit (N=970, 935) | -0.059 Litres | Standard Error 0.0096 |
| Fluticasone Withdrawal | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 6 visit (N=1135, 1135) | -0.011 Litres | Standard Error 0.0062 |
| Fluticasone Withdrawal | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 18 visit (N=1077, 1058) | -0.050 Litres | Standard Error 0.0064 |
| Fluticasone Withdrawal | Change in On-treatment Lung Function as Measured by Trough FEV1 | Week 12 visit (N=1114, 1092) | -0.018 Litres | Standard Error 0.0063 |
Comparison: Week 52 visitp-value: 0.001495% CI: [-0.069, -0.017]Restricted maximum likelihood
Secondary
Change in On-treatment PEFR as Measured by Home Based Spirometry
Change from baseline in on-treatment peak expiratory flow rate (PEFR) as measured by home based spirometry; change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 45 visit (N=830, 815) | -0.368 Litres/sec | Standard Error 0.0297 |
| Fluticasone Maintenance | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 18 visit (N=913, 901) | -0.295 Litres/sec | Standard Error 0.0253 |
| Fluticasone Maintenance | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 52 visit (N=785, 788) | -0.377 Litres/sec | Standard Error 0.0318 |
| Fluticasone Maintenance | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 36 visit (N=854, 845) | -0.352 Litres/sec | Standard Error 0.0278 |
| Fluticasone Maintenance | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 6 visit (N=893, 939) | -0.228 Litres/sec | Standard Error 0.0249 |
| Fluticasone Maintenance | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 12 visit (N=910, 930) | -0.266 Litres/sec | Standard Error 0.0253 |
| Fluticasone Maintenance | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 27 visit (N=863, 843) | -0.319 Litres/sec | Standard Error 0.0273 |
| Fluticasone Withdrawal | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 12 visit (N=910, 930) | -0.290 Litres/sec | Standard Error 0.0252 |
| Fluticasone Withdrawal | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 18 visit (N=913, 901) | -0.435 Litres/sec | Standard Error 0.0254 |
| Fluticasone Withdrawal | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 27 visit (N=863, 843) | -0.430 Litres/sec | Standard Error 0.0274 |
| Fluticasone Withdrawal | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 36 visit (N=854, 845) | -0.473 Litres/sec | Standard Error 0.0278 |
| Fluticasone Withdrawal | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 45 visit (N=830, 815) | -0.490 Litres/sec | Standard Error 0.0298 |
| Fluticasone Withdrawal | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 52 visit (N=785, 788) | -0.538 Litres/sec | Standard Error 0.0318 |
| Fluticasone Withdrawal | Change in On-treatment PEFR as Measured by Home Based Spirometry | Week 6 visit (N=893, 939) | -0.230 Litres/sec | Standard Error 0.0246 |
Comparison: Week 52 visitp-value: 0.000495% CI: [-0.249, -0.073]Restricted maximum likelihood
Secondary
Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI)
Change from baseline in on-treatment physical health status as determined by body mass index (BMI); change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 18 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI) | Week 52 visit (N=1047, 1021) | 0.004 kg/m2 | Standard Error 0.039 |
| Fluticasone Maintenance | Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI) | Week 18 visit (N=1143, 1146) | 0.030 kg/m2 | Standard Error 0.028 |
| Fluticasone Withdrawal | Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI) | Week 18 visit (N=1143, 1146) | 0.040 kg/m2 | Standard Error 0.028 |
| Fluticasone Withdrawal | Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI) | Week 52 visit (N=1047, 1021) | -0.009 kg/m2 | Standard Error 0.039 |
Comparison: Week 52 visitp-value: 0.813795% CI: [-0.122, 0.096]Restricted maximum likelihood
Secondary
Change in On-treatment Physician Global Evaluation
Change from baseline in on-treatment physician global evaluation. The evaluation reflected the physician's opinion of the patient's overall condition and was based on the need for concomitant medication, the number and severity of exacerbations, the severity of cough, the ability to exercise, the amount of wheezing and any other relevant clinical observations. Patients were graded on a scale of 1 (poor) to 8 (excellent). Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 27 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment Physician Global Evaluation | Week 27 visit (N=1113, 1093) | 0.10 units on a scale | Standard Error 0.03 |
| Fluticasone Maintenance | Change in On-treatment Physician Global Evaluation | Week 52 visit (N=1041, 1014) | 0.19 units on a scale | Standard Error 0.03 |
| Fluticasone Withdrawal | Change in On-treatment Physician Global Evaluation | Week 27 visit (N=1113, 1093) | 0.04 units on a scale | Standard Error 0.03 |
| Fluticasone Withdrawal | Change in On-treatment Physician Global Evaluation | Week 52 visit (N=1041, 1014) | 0.08 units on a scale | Standard Error 0.03 |
Comparison: Week 52 visitp-value: 0.022395% CI: [-0.21, -0.02]Restricted maximum likelihood
Secondary
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain
Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Activity domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 27 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain | Week 27 visit (N=1002, 988) | 0.09 units on a scale | Standard Error 0.492 |
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain | Week 52 visit (N=942, 916) | -0.19 units on a scale | Standard Error 0.512 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain | Week 27 visit (N=1002, 988) | 0.85 units on a scale | Standard Error 0.496 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain | Week 52 visit (N=942, 916) | 0.78 units on a scale | Standard Error 0.518 |
Comparison: Week 52 visitp-value: 0.183895% CI: [-0.46, 2.4]Restricted maximum likelihood
Secondary
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain
Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Impact Domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 27 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain | Week 27 visit (N=1004, 998) | -0.78 units on a scale | Standard Error 0.456 |
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain | Week 52 visit (N=946, 921) | -0.08 units on a scale | Standard Error 0.494 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain | Week 52 visit (N=946, 921) | 1.27 units on a scale | Standard Error 0.499 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain | Week 27 visit (N=1004, 998) | 0.35 units on a scale | Standard Error 0.457 |
Comparison: Week 52 visitp-value: 0.055195% CI: [-0.03, 2.72]Restricted maximum likelihood
Secondary
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain
Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Symptoms domain. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 27 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain | Week 27 visit (N=1010, 998) | 0.12 units on a scale | Standard Error 0.583 |
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain | Week 52 visit (N=955, 921) | 0.51 units on a scale | Standard Error 0.593 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain | Week 27 visit (N=1010, 998) | 0.62 units on a scale | Standard Error 0.586 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain | Week 52 visit (N=955, 921) | 1.11 units on a scale | Standard Error 0.602 |
Comparison: Week 52 visitp-value: 0.480495% CI: [-1.06, 2.25]Restricted maximum likelihood
Secondary
Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score
Change from baseline in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores: Total score. Scores range from 0 to 100, with higher scores indicating more limitations. Change was calculated as week score minus baseline score. Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 27 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score | Week 27 visit (N=996, 986) | -0.42 units on a scale | Standard Error 0.398 |
| Fluticasone Maintenance | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score | Week 52 visit (N=939, 913) | -0.07 units on a scale | Standard Error 0.432 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score | Week 27 visit (N=996, 986) | 0.55 units on a scale | Standard Error 0.401 |
| Fluticasone Withdrawal | Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score | Week 52 visit (N=939, 913) | 1.15 units on a scale | Standard Error 0.437 |
Comparison: Week 52 visitp-value: 0.046795% CI: [0.02, 2.43]Restricted maximum likelihood
Secondary
Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale
Change from baseline in on-treatment dyspnoea as measured by the Modified Medical Research Council (MMRC) dyspnoea scale; change was calculated as week score minus baseline score. Negative changes from baseline indicate an improvement in health. Scale from 0 to 4: * 0 = not troubled by breathlessness, except during strenuous exercise * 1 = short of breath when hurrying or walking up a slight hill * 2 = walks slower than contemporaries on the same level because of breathlessness, or has to stop for breath when walking at own pace * 3 = stops for breath after approximately 100 yards, or after a few minutes on the level * 4 = too breathless to leave the house, or breathless when dressing or undressing No breathlessness was given a score of -1 Statistical analysis results are presented only for the week 52 visit as this is the primary timepoint of interest.
Time frame: Baseline and week 18 and 52 visits
Population: Treated set
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Fluticasone Maintenance | Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale | Week 18 visit (N=1140, 1143) | -0.030 units on a scale | Standard Error 0.022 |
| Fluticasone Maintenance | Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale | Week 52 visit (N=1043, 1019) | -0.028 units on a scale | Standard Error 0.024 |
| Fluticasone Withdrawal | Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale | Week 18 visit (N=1140, 1143) | -0.001 units on a scale | Standard Error 0.022 |
| Fluticasone Withdrawal | Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale | Week 52 visit (N=1043, 1019) | 0.035 units on a scale | Standard Error 0.024 |
Comparison: Week 52 visitp-value: 0.063295% CI: [-0.004, 0.131]Restricted maximum likelihood
Secondary
Number of Moderate or Severe On-treatment COPD Exacerbations
Number of moderate or severe on-treatment COPD exacerbations, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined and counted as moderate or severe if ≥1 of the contributing exacerbation events was moderate or severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids. Measured values show adjusted mean event rate.
Time frame: During randomised treatment, up to 488 days
Population: Treated Set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fluticasone Maintenance | Number of Moderate or Severe On-treatment COPD Exacerbations | 0.91 exacerbations per patient-year |
| Fluticasone Withdrawal | Number of Moderate or Severe On-treatment COPD Exacerbations | 0.95 exacerbations per patient-year |
p-value: 0.444195% CI: [0.93, 1.18]Regression, Negative Binomial
Secondary
Number of On-treatment COPD Exacerbations
Number of on-treatment COPD exacerbations of any severity, based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined. Measured values show adjusted event rate.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fluticasone Maintenance | Number of On-treatment COPD Exacerbations | 1.03 exacerbations per patient-year |
| Fluticasone Withdrawal | Number of On-treatment COPD Exacerbations | 1.08 exacerbations per patient-year |
p-value: 0.434295% CI: [0.93, 1.18]Regression, Negative binomial
Secondary
Number of Severe On-treatment COPD Exacerbations
Number of severe on-treatment COPD exacerbations based on a 7-day gap rule: exacerbations where the onset date of the second exacerbation event was ≤7 days after the end date of the first exacerbation event were combined and counted as severe if ≥1 of the contributing exacerbation events was severe. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Measured values show adjusted event rate.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fluticasone Maintenance | Number of Severe On-treatment COPD Exacerbations | 0.20 exacerbations per patient-year |
| Fluticasone Withdrawal | Number of Severe On-treatment COPD Exacerbations | 0.23 exacerbations per patient-year |
p-value: 0.229195% CI: [0.92, 1.45]Regression, Negative Binomial
Secondary
Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation
Presence (yes vs no) of at least one moderate or severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. Exacerbations were considered moderate if they required prescription of antibiotics and/or systemic steroids.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Maintenance | Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation | 44.2 percentage of participants |
| Fluticasone Withdrawal | Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation | 46.7 percentage of participants |
p-value: 0.2269Fisher Exact
Secondary
Proportion of Patients With at Least One On-treatment COPD Exacerbation
Presence (yes vs no) of at least one on-treatment COPD exacerbation of any severity, displayed as a percentage.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Maintenance | Proportion of Patients With at Least One On-treatment COPD Exacerbation | 46.9 percentage of participants |
| Fluticasone Withdrawal | Proportion of Patients With at Least One On-treatment COPD Exacerbation | 49.0 percentage of participants |
p-value: 0.3155Fisher Exact
Secondary
Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation.
Presence (yes vs no) of at least one severe on-treatment COPD exacerbation, displayed as a percentage. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Maintenance | Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation. | 13.4 percentage of participants |
| Fluticasone Withdrawal | Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation. | 15.2 percentage of participants |
p-value: 0.2083Fisher Exact
Secondary
Severity of On-treatment COPD Exacerbations
Severity of on-treatment COPD exacerbations: for each patient, the worst applicable category was taken (i.e. none, mild, moderate or severe)
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Fluticasone Maintenance | Severity of On-treatment COPD Exacerbations | None and patient discontinued randomised treatment | 10.2 percentage of participants |
| Fluticasone Maintenance | Severity of On-treatment COPD Exacerbations | Moderate | 30.8 percentage of participants |
| Fluticasone Maintenance | Severity of On-treatment COPD Exacerbations | Mild | 2.7 percentage of participants |
| Fluticasone Maintenance | Severity of On-treatment COPD Exacerbations | Severe | 13.4 percentage of participants |
| Fluticasone Maintenance | Severity of On-treatment COPD Exacerbations | None and patient completed randomised treatment | 42.9 percentage of participants |
| Fluticasone Withdrawal | Severity of On-treatment COPD Exacerbations | Severe | 15.2 percentage of participants |
| Fluticasone Withdrawal | Severity of On-treatment COPD Exacerbations | None and patient completed randomised treatment | 41.2 percentage of participants |
| Fluticasone Withdrawal | Severity of On-treatment COPD Exacerbations | None and patient discontinued randomised treatment | 9.8 percentage of participants |
| Fluticasone Withdrawal | Severity of On-treatment COPD Exacerbations | Mild | 2.3 percentage of participants |
| Fluticasone Withdrawal | Severity of On-treatment COPD Exacerbations | Moderate | 31.5 percentage of participants |
Secondary
Time to First On-treatment COPD Exacerbation
Time to first on-treatment COPD exacerbation of any severity. The measure type displays the 25th percentile and its 95% confidence interval.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Maintenance | Time to First On-treatment COPD Exacerbation | 365.0 days |
| Fluticasone Withdrawal | Time to First On-treatment COPD Exacerbation | 346.0 days |
p-value: 0.556295% CI: [0.923, 1.16]Chi-squared
Secondary
Time to First Severe On-treatment COPD Exacerbation
Time to first severe on-treatment COPD exacerbation. Exacerbations were considered severe if the patient was held and treated for an acute respiratory condition in an urgent care department or an observation unit for \>6 hours, the patient was treated at home by a mobile urgent care team or the patient was admitted to hospital. The measure type displays the 25th percentile and its 95% confidence interval.
Time frame: During randomised treatment, up to 488 days
Population: Treated set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fluticasone Maintenance | Time to First Severe On-treatment COPD Exacerbation | NA days |
| Fluticasone Withdrawal | Time to First Severe On-treatment COPD Exacerbation | 419.0 days |
p-value: 0.084995% CI: [0.975, 1.481]Chi-squared