Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

Phase 4

Completed

Conditions: Pulmonary Disease, Chronic Obstructive

Interventions: Drug: tiotropium inhalation
Drug: salmeterol xinafoate
Drug: fluticasone propionate
Drug: placebo matched for fluticasone propionate

Registration Number: NCT00975195

Lead Sponsor: Boehringer Ingelheim

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 2488

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
fluticasone high dose	salmeterol xinafoate	fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate
fluticasone high dose	tiotropium inhalation	fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate
fluticasone medium & low doses	tiotropium inhalation	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone medium & low doses	salmeterol xinafoate	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone medium & low doses	placebo matched for fluticasone propionate	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone medium & low doses	fluticasone propionate	fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
fluticasone high dose	fluticasone propionate	fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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)
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.
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.
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.
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.
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.
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 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.
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.
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 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.
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 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.
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: 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 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 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.
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 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 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.

Trial Locations

Locations (222): 352.2046.61006 Boehringer Ingelheim Investigational Site
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Concord, New South Wales, Australia
352.2046.61001 Boehringer Ingelheim Investigational Site
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Glebe, New South Wales, Australia
352.2046.61002 Boehringer Ingelheim Investigational Site
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Westmead, New South Wales, Australia
352.2046.61004 Boehringer Ingelheim Investigational Site
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Daw Park, South Australia, Australia
352.2046.61003 Boehringer Ingelheim Investigational Site
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Toorak Gardens, South Australia, Australia
352.2046.61005 Boehringer Ingelheim Investigational Site
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Woodville, South Australia, Australia
352.2046.32002 Boehringer Ingelheim Investigational Site
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Bruxelles, Belgium
352.2046.32016 Boehringer Ingelheim Investigational Site
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Bruxelles, Belgium
352.2046.32015 Boehringer Ingelheim Investigational Site
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Eupen, Belgium
352.2046.32017 Boehringer Ingelheim Investigational Site
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Gilly, Belgium
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352.2046.61006 Boehringer Ingelheim Investigational Site
🇦🇺Concord, New South Wales, Australia