Modification Of Disease Outcome In COPD

Chronic Obstructive Pulmonary Disease Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00158847
• Other study ID #: SCO30001
• Secondary ID: SER9804 / Glucol
• Status: Terminated
• Phase: Phase 4
• First received: September 8, 2005
• Last updated: January 10, 2006
• Start date: April 2000
• Est. completion date: May 2005

Study information

• Verified date: January 2005
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

The hypothesis to be tested of this study is that treatment with fluticasone propionate leads to an initial improvement in symptoms, quality of life and lungfunction and a reduction in airways hyperresponsiveness. The continued decline of lungfunction in COPD may not be influenced by longer lasting treatment. Addition of salmeterol will augment the initial benefits of fluticasone without changing the longterm decline in lungfunction.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 200
• Est. completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 75 Years

Eligibility

Inclusion criteria:

• COPD patients with > 10 pack years.

• Written informed consent.

• Able to complete a diary card.

• At least one of the following symptoms: chronic cough, chronic sputum production, frequent exacerbations, or dyspnoea at exertion.

• Postbronchodilator FEV1 below 90% confidence interval of predicted and postbronchodilator FEV1/FVC below 90% confidence interval of predicted.

Exclusion criteria:

• No oral corticosteroids 3 months prior to the study or maintenance treatment with corticostroids 6 months prior to the study.

• No history of asthma, lung diseases other than COPD, other diseases likely to interfere with the study.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• fluticasone 500 mcg

• fluticasone 500 mcg + salmeterol 50 mcg

Locations

Country	Name	City	State
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden

Sponsors (5)

Lead Sponsor	Collaborator
Leiden University Medical Center	Academisch Ziekenhuis Groningen, GlaxoSmithKline, Netherlands Organisation for Scientific Research, The Netherlands Asthma Foundation

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Lapperre TS, Snoeck-Stroband JB, Gosman MM, Stolk J, Sont JK, Jansen DF, Kerstjens HA, Postma DS, Sterk PJ; Groningen and Leiden Universities Corticosteroids in Obstructive Lung Disease Study Group. Dissociation of lung function and airway inflammation in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004 Sep 1;170(5):499-504. Epub 2004 Jun 1. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Secondary	Clinical: symptoms, exacerbations, quality of life, lung function, 6 min walking test. Inflammation: markers in sputum and BAL, profile of epithelial cells, remodeling.