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Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

Primary Purpose

Pulmonary Disease, Chronic Obstructive

Status

Completed

Phase

Phase 4

Locations

International

Study Type

Interventional

Intervention

tiotropium inhalation

salmeterol xinafoate

fluticasone propionate

placebo matched for fluticasone propionate

About this trial

This is an interventional treatment trial for Pulmonary Disease, Chronic Obstructive

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

Male or female aged 40 years or more
Severe to very severe chronic obstructive pulmonary disease (COPD)
Current or ex-smoker with smoking history of at least 10 pack years
At least one documented exacerbation of COPD in previous year

Exclusion criteria:

Significant diseases other than COPD; significant alcohol or drug abuse
Current clinical diagnosis of asthma requiring steroid treatment
History of thoracotomy with pulmonary resection
Regular use of daytime oxygen
Recent history (within 3 months) of myocardial infarction
Recent (within 6 weeks) respiratory infection or COPD exacerbation
Recent (within 6 weeks) treatment with systemic corticosteroids at doses in excess of 5milligram / day
Recent (within 3 months) unstable or life-threatening cardiac arrhythmia requiring intervention
Recent (within 1 year) hospitalisation for cardiac failure
Malignancy requiring chemotherapy or radiotherapy
Clinical diagnosis of bronchiectasis
Pregnant or nursing women
Known hypersensitivity to study drugs
Current or recent (within 30 days) participation in another clinical study
Current participation in or recent completion (within 4 weeks) of a pulmonary rehabilitation program

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

fluticasone high dose

fluticasone medium & low doses

Arm Description

fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate

fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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 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.

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.

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 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.

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.

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.

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)

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Full Information

NCT ID

NCT00975195

First Posted

September 10, 2009

Last Updated

February 9, 2015

Sponsor

Boehringer Ingelheim

1. Study Identification

Unique Protocol Identification Number

NCT00975195

Brief Title

Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

February 2015

Overall Recruitment Status

Completed

Study Start Date

February 2009 (undefined)

Primary Completion Date

July 2013 (Actual)

Study Completion Date

July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Boehringer Ingelheim

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pulmonary Disease, Chronic Obstructive

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

2488 (Actual)

8. Arms, Groups, and Interventions

Arm Title

fluticasone high dose

Arm Type

Experimental

Arm Description

fluticasone priopionate high dose and tiotropium inhalation and salmeterol xinafoate

Arm Title

fluticasone medium & low doses

Arm Type

Experimental

Arm Description

fluticasone priopionate medium and high doses; and tiotropium inhalation; and salmeterol xinafoate; and placebo matched to fluticasone priopionate

Intervention Type

Drug

Intervention Name(s)

tiotropium inhalation

Intervention Type

Drug

Intervention Name(s)

salmeterol xinafoate

Intervention Type

Drug

Intervention Name(s)

fluticasone propionate

Intervention Type

Drug

Intervention Name(s)

placebo matched for fluticasone propionate

Primary Outcome Measure Information:

Title

Time to First Moderate or Severe On-treatment COPD Exacerbation

Description

Time Frame