Modification Of Disease Outcome In COPD
|ClinicalTrials.gov Identifier: NCT00158847|
Recruitment Status : Terminated
First Posted : September 12, 2005
Last Update Posted : January 20, 2006
|Condition or disease||Intervention/treatment||Phase|
|Chronic Obstructive Pulmonary Disease||Drug: fluticasone 500 mcg Drug: fluticasone 500 mcg + salmeterol 50 mcg||Phase 4|
Aim The primary aim of this study was to investigate whether short-term treatment with inhaled corticosteroids in COPD results in greater improvements in airway pathology, thereby leading to larger clinical benefits, than continuous long-term treatment. To that end, the outcome variables included features of airways inflammation and remodelling as well as clinical symptoms, exacerbations, quality of life, decline in FEV1, bronchial responsiveness, and pharmaco-economics. The secondary aim of the study was to examine the histopathological and clinical benefits of the combined treatment with an inhaled steroid and a long-acting ß2-agonist in COPD.
Methods Patients. Patients with COPD (45-75 yr, >10 pckyr) not using inhaled steroids for the past 3 months were recruited.
Design. In a prospective, longitudinal, double blind, 4-arm study, the patients were followed during 2.5 years (Figure 1). They were treated with high dose inhaled corticosteroids (500 g fluticasone bid), combined inhaled steroids+long-acting ß2-agonist (500 µg fluticasone+50 µg salmeterol) or placebo for 6 months. Half of the patients in the steroid group continued their treatment with steroids for another 2 years, whereas the other half received placebo. The combination therapy and placebo groups remained unaltered treatment up to 2.5 years.
Measurements. Symptoms, exacerbations, QOL questionnaires and spirometry were monitored every 3 months. Peripheral blood eosinophils, IgE, exhaled NO, bodyplethysmography, CO-diffusion capacity, PC20 methacholine, sputum induction and bronchoscopy were performed at 0, 6, and 30 months. In BAL and induced sputum we are measuring cell differentials and their state of activation. Immunohistochemistry is being performed in bronchial biopsy specimens, staining for markers on infiltrative and resident cells, and morphometric analysis will allow airway remodelling to be quantified, by using a computerized image analysis system. The effects of treatment will be analyzed by relating the observed changes in clinical and pathophysiological outcome, to those in cellular and histological outcome by using linear mixed statistical models.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||200 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Modification of Disease Outcome in COPD. Shortterm Versus Longterm Treatment With Inhaled Corticosteroids, Either or Not Combined With a Long-Acting Beta2-Agonist.|
|Study Start Date :||April 2000|
|Estimated Study Completion Date :||May 2005|
- Inflammation: localisation, numbers and profile of neutrophils, eosinophils, macrophages, and CD8+T cells in bronchial biopsy specimens after 6 months and 2.5 years treatment.
- Clinical: symptoms, exacerbations, quality of life, lung function, 6 min walking test. Inflammation: markers in sputum and BAL, profile of epithelial cells, remodeling.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00158847
|University Medical Center Groningen|
|Groningen, Netherlands, 9700 RB|
|Leiden University Medical Center|
|Leiden, Netherlands, 2300 RC|
|Principal Investigator:||Peter J. Sterk, MD, PhD||Leiden University Medical Center|