Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00975195
First received: September 10, 2009
Last updated: February 9, 2015
Last verified: February 2015

September 10, 2009
February 9, 2015
February 2009
July 2013   (final data collection date for primary outcome measure)
Time to First Moderate or Severe On-treatment COPD Exacerbation [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]
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.
The primary efficacy endpoint is time to first COPD exacerbation. [ Time Frame: 48 weeks ]
Complete list of historical versions of study NCT00975195 on ClinicalTrials.gov Archive Site
  • Number of Moderate or Severe On-treatment COPD Exacerbations [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]

    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.

  • Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]

    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 [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]

    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. [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]

    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 [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: During randomised treatment, up to 488 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 6, 12, 18 and 52 visits ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 18 and 52 visits ] [ Designated as safety issue: No ]

    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 Physical Health Status as Determined by Body Mass Index (BMI) [ Time Frame: Baseline and week 18 and 52 visits ] [ Designated as safety issue: No ]
    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 Exercise Capacity Measured by Six-minute Walk Test (6-MWT) [ Time Frame: Baseline and week 18 and 52 visits ] [ Designated as safety issue: No ]
    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 BODE Index [ Time Frame: Baseline and week 18 and 52 visits ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 12, 18 and 52 visits ] [ Designated as safety issue: No ]

    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: Cough Symptoms Domain [ Time Frame: Baseline and week 12, 18 and 52 visits ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and week 12, 18 and 52 visits ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and week 12, 18 and 52 visits ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 6, 12, 18, 27, 36, 45 and 52 visits ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and week 27 and 52 visits ] [ Designated as safety issue: No ]

    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: Impact Domain [ Time Frame: Baseline and week 27 and 52 visits ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and week 27 and 52 visits ] [ Designated as safety issue: No ]

    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 St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score [ Time Frame: Baseline and week 27 and 52 visits ] [ Designated as safety issue: No ]

    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 [ Time Frame: Baseline and week 27 and 52 visits ] [ Designated as safety issue: No ]

    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.

Breathlessness, exercise endurance, health related quality of life Number and severity of COPD exacerbations Changes in inflammatory markers [ Time Frame: 48 weeks ]
Not Provided
Not Provided
 
Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease
A Randomised, Double-blind, Active-controlled Study to Evaluate the Impact of Stepwise Withdrawal of Inhaled Corticosteroid Treatment in Patients With Severe to Very Severe Chronic Obstructive Pulmonary Disease (COPD) on Optimized Bronchodilator Therapy

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.

Not Provided
Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Pulmonary Disease, Chronic Obstructive
  • Drug: tiotropium inhalation
  • Drug: salmeterol xinafoate
  • Drug: fluticasone propionate
  • Drug: placebo matched for fluticasone propionate
  • Experimental: fluticasone high dose
    fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate
    Interventions:
    • Drug: tiotropium inhalation
    • Drug: salmeterol xinafoate
    • Drug: fluticasone propionate
  • Experimental: fluticasone medium & low doses
    fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate
    Interventions:
    • Drug: tiotropium inhalation
    • Drug: salmeterol xinafoate
    • Drug: fluticasone propionate
    • Drug: placebo matched for fluticasone propionate
Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, Towse L, Finnigan H, Dahl R, Decramer M, Chanez P, Wouters EF, Calverley PM; WISDOM Investigators. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014 Oct 2;371(14):1285-94. doi: 10.1056/NEJMoa1407154. Epub 2014 Sep 8.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
2488
July 2013
July 2013   (final data collection date for primary outcome measure)

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
Both
40 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Belgium,   Brazil,   Bulgaria,   China,   Denmark,   France,   Germany,   Greece,   Hungary,   Italy,   Netherlands,   New Zealand,   Philippines,   Poland,   Russian Federation,   South Africa,   Spain,   Taiwan,   Tunisia,   Turkey,   Ukraine,   United Kingdom
Switzerland
 
NCT00975195
352.2046, 2007-002522-29
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
February 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP