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: April 30, 2014
Last verified: November 2013
  Purpose

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.


Condition Intervention Phase
Pulmonary Disease, Chronic Obstructive
Drug: Tiotropium +salmeterol+ fluticasone high dose
Drug: Tiotropium+salmeterol+ fluticasone high,med, low, placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Time to first moderate or severe on-treatment COPD exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of moderate or severe on-treatment COPD exacerbations [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Severity of on-treatment COPD exacerbations [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Changes in on-treatment lung function as measured by trough forced expiratory volume in one second (FEV1) [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in on-treatment dyspnoea as measured by the Modified Medical Research Council (MMRC) dyspnoea scale [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in on-treatment exercise capacity measured by six-minute walk test (6-MWT) [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in on-treatment St Georges Respiratory Questionnaire (SGRQ) scores. [ Time Frame: up tp 52 weeks ] [ Designated as safety issue: No ]
  • Changes in on-treatment serum biomarkers adiponectin, leptin, C-reactive protein, IL-6, IL-8, TNF-α, fibrinogen, sICAM-1, serum amyloid A and B-type BNP, procalcitonin [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in sputum cellularity [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with at least one moderate or severe on-treatment COPD exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Time to first severe on-treatment COPD exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Number of severe on-treamtent COPD exacerbation [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with at least one severe on-treatment COPD exacerbation. [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Time to first on-treatment COPD exacerbation (any severity). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Number of on-treatment COPD exacerbations (any severity). [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients with at least one on-treatment COPD exacerbation (any severity) [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  • Changes in on-treatment physical health status as determined by body mass index (BMI) [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in on-treatment BODE index [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in on-treatment cough and expectoration as measured by the cough and sputum assessment questionnaire (CASA-Q) (selected sites only) [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in on-treatment lung function (FEV1, FVC and and peak expiratory flow rate (PEFR)) as measured by home based spirometry [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Changes in on-treatment physician global evaluation [ Time Frame: week 52 ] [ Designated as safety issue: No ]
  • Change in total lung capacity (TLC), functional residual capacity (FRC) and inspiratory capacity (IC) as determined by body plethysmograph [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
  • Changes in exhaled nitric oxide (NO). [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
  • Changes in arterialised blood gases (PaO2 and PaCO2). [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
  • Changes in diffusing capacity of carbon monoxide (DLCO). [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
  • Major Adverse Cardiovascular Events (MACE) [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]
  • Fatal MACE [ Time Frame: up uo 52 weeks ] [ Designated as safety issue: Yes ]
  • Stroke [ Time Frame: up to 52 weeks ] [ Designated as safety issue: Yes ]
  • Incidence of adverse events [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
  • Vital Signs [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
  • Pneumonia [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]
  • Vital status [ Time Frame: up to 52 weeks ] [ Designated as safety issue: No ]

Enrollment: 2488
Study Start Date: February 2009
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fluticasone maintenance Drug: Tiotropium +salmeterol+ fluticasone high dose
Placebo Comparator: Fluticasone withdrawal Drug: Tiotropium+salmeterol+ fluticasone high,med, low, placebo

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00975195

  Show 222 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00975195     History of Changes
Other Study ID Numbers: 352.2046, 2007-002522-29
Study First Received: September 10, 2009
Last Updated: April 30, 2014
Health Authority: Australia: Dept of Health and Ageing Therapeutic Goods Admin
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency, BG-1504 Sofia
China: Food and Drug Administration
Denmark: The Danish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Great Britain: MHRA
Greece: Ethics Committee
Hungary: National Institute of Pharmacy, H-1051 Budapest
Italy: Ethics Committee
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Multicentre Ethics Committee/Medsafe
Philippines: Bureau of Food and Drugs
Poland: Registration Medicinal Product Medical Device Biocidal Product
Russia: Ministry of Healthcare and Social Development of Russian Federation, Moscow
South Africa: Medicines Control Council
Spain: Spanish Agency of Medicines
Taiwan: Department of Health
Tunisia: Office of Pharmacies and Medicines
Turkey: Ministry of Health Central Ethics Committee
Ukraine: Ministry of Health Care of Ukraine (MoH of Ukraine)

Additional relevant MeSH terms:
Chronic Disease
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Lung Diseases, Obstructive
Disease Attributes
Pathologic Processes
Respiratory Tract Diseases
Salmeterol
Fluticasone
Tiotropium
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Dermatologic Agents
Anti-Allergic Agents
Anti-Inflammatory Agents
Parasympatholytics
Cholinergic Antagonists

ClinicalTrials.gov processed this record on July 22, 2014