Stepwise withdrawal of inhaled corticosteroids in COPD patients receiving dual bronchodilation: WISDOM study design and rationale.
Long-acting bronchodilators in combination with inhaled corticosteroids (ICS) are recommended to decrease the risk of recurrent exacerbations in patients with Global initiative for chronic Obstructive Lung Disease (GOLD) stage 3-4 chronic obstructive pulmonary disease (COPD). There is increasing concern about the clinical benefit and long-term safety of ICS use in COPD patients. The WISDOM (Withdrawal of Inhaled Steroids During Optimised bronchodilator Management) study (NCT00975195) aims to evaluate the need for ICS use via stepwise withdrawal of ICS in COPD patients (GOLD 3-4 with a history of at least one exacerbation during the 12-month period prior to screening) receiving dual bronchodilation. During the 6-week run-in period, 2456 patients receive tiotropium 18 μg once daily, salmeterol 50 μg twice daily and fluticasone 500 μg twice daily. In a randomized, double-blind, parallel-group, active-controlled fashion, one group of patients continues to receive tiotropium, salmeterol and fluticasone, while the second group initiates stepwise withdrawal of fluticasone. The primary end point is time to first moderate or severe exacerbation following randomized treatment over 52 weeks. Lung function, symptoms and safety are also assessed. A sub-study aims to identify sub-populations and markers of steroid need. This study will determine the benefit of continued ICS therapy in combination with dual long-acting bronchodilators in COPD.
Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany. Electronic address: magnussen@pulmoresearch.de.
Helgo
H
Magnussen
Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany.
Henrik
H
Watz
Pulmonary Research Institute at Lung Clinic Grosshansdorf, Airway Research Center North, Member of the German Center for Lung Research, Grosshansdorf, Germany.
Anne
A
Kirsten
Department of Respiratory Diseases, University of Leuven, Leuven, Belgium.
Marc
M
Decramer
Odense University Hospital, Odense, Denmark.
Ronald
R
Dahl
Institute of Ageing and Chronic Disease, University Hospital Aintree, Liverpool, UK.
Peter M A
PM
Calverley
Clinical Research Department, Boehringer Ingelheim (UK), Berkshire, UK.
Lesley
L
Towse
Biometry and Data Management Department, Boehringer Ingelheim (UK), Berkshire, UK.
Helen
H
Finnigan
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; Department of Sports Medicine, University of Tübingen, Tübingen, Germany.
Kay
K
Tetzlaff
Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Bernd
B
Disse
D000280:Administration, Inhalation; D000328:Adult; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D012107:Research Design; D016896:Treatment Outcome; D014797:Vital Capacity / Q000187:drug effects; D028761:Withholding Treatment
D001993:Bronchodilator Agents; D005938:Glucocorticoids
Chronic obstructive pulmonary disease; Dual bronchodilation; Exacerbation; Withdrawal of inhaled corticosteroid