Phase 4 N=2,488 Randomized Double-blind Treatment

Inhaled Corticosteroid Withdrawal in Patients With Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive

Bottom Line

View on ClinicalTrials.gov: NCT00975195 ↗

Enrolled (actual)

2,488

Serious AEs

23.8%

Results posted

Feb 2015

Primary outcome: Primary: Time to First Moderate or Severe On-treatment COPD Exacerbation — 107.0; 110.0 days — p=0.3497

Study Design & Population

Study type: Interventional
Phase: Phase 4
Interventions: tiotropium inhalation (Drug); salmeterol xinafoate (Drug); fluticasone propionate (Drug); placebo matched for fluticasone propionate (Drug)
Age: Adult, Older Adult · 40+ yrs
Sex: All
Sponsor: Boehringer Ingelheim
Primary completion: Jul 2013

Outcome Measures

Outcome	Result	p-value
PRIMARY Time to First Moderate or Severe On-treatment COPD Exacerbation	107.0; 110.0	0.3497
SECONDARY Number of Moderate or Severe On-treatment COPD Exacerbations	0.91; 0.95	0.4441
SECONDARY Proportion of Patients With ≥1 Moderate or Severe On-treatment COPD Exacerbation	44.2; 46.7	0.2269
SECONDARY Time to First Severe On-treatment COPD Exacerbation	NA; 419.0	0.0849
SECONDARY Number of Severe On-treatment COPD Exacerbations	0.20; 0.23	0.2291
SECONDARY Proportion of Patients With at Least One Severe On-treatment COPD Exacerbation.	13.4; 15.2	0.2083
SECONDARY Time to First On-treatment COPD Exacerbation	365.0; 346.0	0.5562
SECONDARY Number of On-treatment COPD Exacerbations	1.03; 1.08	0.4342
SECONDARY Proportion of Patients With at Least One On-treatment COPD Exacerbation	46.9; 49.0	0.3155
SECONDARY Severity of On-treatment COPD Exacerbations	42.9; 41.2; 10.2; 9.8; 2.7; 2.3	—
SECONDARY Change in On-treatment Lung Function as Measured by Trough FEV1	-0.009; -0.011; -0.011; -0.018; -0.011; -0.050	0.0014 sig
SECONDARY Changes in On-treatment Dyspnoea as Measured by the Modified Medical Research Council (MMRC) Dyspnoea Scale	-0.030; -0.001; -0.028; 0.035	0.0632
SECONDARY Change in On-treatment Physical Health Status as Determined by Body Mass Index (BMI)	0.030; 0.040; 0.004; -0.009	0.8137
SECONDARY Change in On-treatment Exercise Capacity Measured by Six-minute Walk Test (6-MWT)	3.89; 1.94; 3.94; 0.42	0.2663
SECONDARY Change in On-treatment BODE Index	-0.06; 0.06; -0.03; 0.14	0.0033 sig
SECONDARY Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Impact Domain	-1.65; -1.24; -2.87; -3.71; -4.51; -5.54	0.4914
SECONDARY Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Cough Symptoms Domain	-0.32; -0.85; -1.47; -3.34; -1.69; -3.26	0.3490
SECONDARY Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Impact Domain	-2.26; -1.63; -2.38; -3.31; -4.29; -4.15	0.9262
SECONDARY Change in On-treatment Cough and Expectoration as Measured by the CASA-Q: Sputum Symptoms Domain	-1.36; -1.24; -2.71; -1.93; -5.10; -2.45	0.1241
SECONDARY Change in On-treatment FEV1 as Measured by Home Based Spirometry	-0.049; -0.053; -0.050; -0.056; -0.051; -0.093	<0.0001 sig
SECONDARY Change in On-treatment FVC as Measured by Home Based Spirometry	-0.116; -0.089; -0.113; -0.105; -0.122; -0.124	0.0855
SECONDARY Change in On-treatment PEFR as Measured by Home Based Spirometry	-0.228; -0.230; -0.266; -0.290; -0.295; -0.435	0.0004 sig
SECONDARY Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Activity Domain	0.09; 0.85; -0.19; 0.78	0.1838
SECONDARY Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Impact Domain	-0.78; 0.35; -0.08; 1.27	0.0551
SECONDARY Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Symptoms Domain	0.12; 0.62; 0.51; 1.11	0.4804
SECONDARY Change in On-treatment St Georges Respiratory Questionnaire (SGRQ) Scores: Total Score	-0.42; 0.55; -0.07; 1.15	0.0467 sig
SECONDARY Change in On-treatment Physician Global Evaluation	0.10; 0.04; 0.19; 0.08	0.0223 sig

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.

Eligibility Criteria

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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT00975195). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.