Clinical trial NCT00496470: Evaluation of Efficacy and Safety of Symbicort® as an add-on Treatment to Spiriva® in Patients With Severe COPD.
Official title: A 12-week, Double-blind, Randomised, Parallel Group, Multi-centre, Study to Evaluate Efficacy and Safety of Budesonide/Formoterol (Symbicort Turbuhaler®) 320/9 µg One Inhalation Twice Daily on Top of Tiotropium (Spiriva®) 18 µg One Inhalation Once Daily
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Obstructive Pulmonary Disease, COPD
Keywords: Chronic Obstructive Pulmonary Disease, COPD
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2007-07-04
Enrollment: 660
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the effect of combined treatment with Symbicort and Spiriva, in terms of improvement of lung function, symptoms and inflammatory markers, in patients with severe COPD.


Eligibility criteria: Inclusion Criteria:

* \>=40 years of age, diagnosed COPD with symptoms \>=2 years, pre-bronchodilatory FEV1 \<=50% of PN

Exclusion Criteria:

* Current respiratory tract disorder other than COPD, history of asthma or rhinitis, significant or unstable cardiovascular disorder

Primary outcomes:
measure: Forced Expiratory Volume in 1 Second (FEV1) Pre-dose
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose
timeFrame: Baseline to 12 weeks
measure: Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose
timeFrame: Baseline to 12 weeks
measure: Forced Vital Capacity (FVC) Pre-dose
timeFrame: Baseline to 12 weeks
measure: Forced Vital Capacity (FVC) 5 Minutes Post-dose
timeFrame: Baseline to 12 weeks
measure: Forced Vital Capacity (FVC) 60 Minutes Post-dose
timeFrame: Baseline to 12 weeks
measure: Inspiratory Capacity (IC) Pre-dose
timeFrame: Baseline to 12 weeks
measure: Inspiratory Capacity (IC) 60 Minutes Post-dose
timeFrame: Baseline to 12 weeks
measure: St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score
timeFrame: Baseline and 12 weeks
measure: Morning Peak Expiratory Flow (PEF) Pre-dose
timeFrame: Baseline to 12 weeks
measure: Evening Peak Expiratory Flow (PEF) Pre-dose
timeFrame: Baseline to 12 weeks
measure: Morning Peak Expiratory Flow (PEF) 5 Min Post-dose
timeFrame: Baseline to 12 weeks
measure: Morning Peak Expiratory Flow (PEF) 15 Min Post-dose
timeFrame: Baseline to 12 weeks
measure: Morning Diary FEV1 Pre-dose
timeFrame: Baseline to 12 weeks
measure: Evening Diary FEV1, Pre-dose
timeFrame: Baseline to 12 weeks
measure: Morning Diary FEV1, 5 Minutes Post-dose
timeFrame: Baseline to 12 weeks
measure: Morning Diary FEV1, 15 Minutes Post-dose
timeFrame: Baseline to 12 weeks
measure: Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose
timeFrame: Baseline to 12 weeks
measure: GCSQ Score, 5 Minutes Post-dose
timeFrame: Baseline to 12 weeks
measure: GCSQ Score, 15 Minutes Post-dose
timeFrame: Baseline to 12 weeks
measure: Capacity of Day Living in the Morning (CDLM) Score
timeFrame: Baseline to 12 weeks
measure: Use of Rescue Medication, Night
timeFrame: Baseline to 12 weeks
measure: Use of Rescue Medication, Morning
timeFrame: Baseline to 12 weeks
measure: Use of Rescue Medication, Day
timeFrame: Baseline to 12 weeks
measure: Use of Rescue Medication, Total
timeFrame: Baseline to 12 weeks
measure: COPD Symptoms, Breathing Score
timeFrame: Baseline to 12 weeks
measure: COPD Symptoms, Sleeping Score
timeFrame: Baseline to 12 weeks
measure: COPD Symptoms, Chest Score
timeFrame: Baseline to 12 weeks
measure: COPD Symptoms, Cough Score
timeFrame: Baseline to 12 weeks
measure: Severe COPD Exacerbations
timeFrame: 12 weeks
measure: Serum High-sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline to 12 weeks
measure: Serum Interleukin 6 (IL-6)
timeFrame: Baseline to 12 weeks
measure: Serum Interleukin 8 (IL-8)
timeFrame: Baseline to 12 weeks
measure: Serum Monocyte Chemoattractant Protein-1 (MCP-1)
timeFrame: Baseline to 12 weeks
measure: Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha)
timeFrame: Baseline to 12 weeks
measure: Serum Tumor Necrosis Factor-alpha (TNF-alpha)
timeFrame: Baseline to 12 weeks
measure: Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
timeFrame: Baseline to 12 weeks
Other outcomes:
Locations:
city: Concord
country: Australia
facility: Research Site
state: New South Wales
city: Sydney
country: Australia
facility: Research Site
state: New South Wales
city: Auchenflower
country: Australia
facility: Research Site
state: Queensland
city: Carina Heights
country: Australia
facility: Research Site
state: Queensland
city: North Mackay
country: Australia
facility: Research Site
state: Queensland
city: Adelaide
country: Australia
facility: Research Site
state: South Australia
city: Daw Park
country: Australia
facility: Research Site
state: South Australia
city: Clayton
country: Australia
facility: Research Site
state: Victoria
city: Malvern
country: Australia
facility: Research Site
state: Victoria
city: Nedlands
country: Australia
facility: Research Site
state: Western Australia
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Winnipeg
country: Canada
facility: Research Site
state: Manitoba
city: St. John's
country: Canada
facility: Research Site
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Mississauga
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: La Malbaie
country: Canada
facility: Research Site
state: Quebec
city: Trois-rivires
country: Canada
facility: Research Site
state: Quebec
city: Saskatoon
country: Canada
facility: Research Site
state: Saskatchewan
city: Quebec
country: Canada
facility: Research Site
city: Chamalieres
country: France
facility: Research Site
city: Creil
country: France
facility: Research Site
city: Ferolles Attilly
country: France
facility: Research Site
city: Grasse
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Marseille Cedex 06
country: France
facility: Research Site
city: Metz
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Perpignan
country: France
facility: Research Site
city: Poitiers Cedex
country: France
facility: Research Site
city: Selestat
country: France
facility: Research Site
city: St Laurent Du Var
country: France
facility: Research Site
city: Strasbourg Cedex
country: France
facility: Research Site
city: Toulouse Cedex 9
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Gelsenkirchen
country: Germany
facility: Research Site
city: Hagen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Kassel
country: Germany
facility: Research Site
city: Koblenz
country: Germany
facility: Research Site
city: Leipzig
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Potsdam
country: Germany
facility: Research Site
city: Aszod
country: Hungary
facility: Research Site
city: Baja
country: Hungary
facility: Research Site
city: Balassagyarmat
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Cegled
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Fuzesabony
country: Hungary
facility: Research Site
city: Jaszbereny
country: Hungary
facility: Research Site
city: Komlo
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Torokbalint
country: Hungary
facility: Research Site
city: Vásárosnamény
country: Hungary
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Chrzanów
country: Poland
facility: Research Site
city: Ilawa
country: Poland
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lomza
country: Poland
facility: Research Site
city: Piekary Slaskie
country: Poland
facility: Research Site
city: Tarnow
country: Poland
facility: Research Site
city: Turek
country: Poland
facility: Research Site
city: Zawadzkie
country: Poland
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Liptovsky Hradok
country: Slovakia
facility: Research Site
city: Lucenec
country: Slovakia
facility: Research Site
city: Nove Mesto Nad Vahom
country: Slovakia
facility: Research Site
city: Nove Zamky
country: Slovakia
facility: Research Site
city: Piestany
country: Slovakia
facility: Research Site
city: Poprad
country: Slovakia
facility: Research Site
city: Povazska Bystrica
country: Slovakia
facility: Research Site
city: Presov
country: Slovakia
facility: Research Site
city: Prievidza
country: Slovakia
facility: Research Site
city: Revuca
country: Slovakia
facility: Research Site
city: Trnava
country: Slovakia
facility: Research Site
city: Zilina
country: Slovakia
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
state: Cataluna
city: Reus (tarragona)
country: Spain
facility: Research Site
state: Cataluna
city: Madrid
country: Spain
facility: Research Site
state: Comunidad de Madrid
city: Requena (valencia)
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Valencia
country: Spain
facility: Research Site
state: Comunidad Valenciana
city: Pontevedra
country: Spain
facility: Research Site
state: Galicia
city: Lindesberg
country: Sweden
facility: Research Site
state: Orebro Lan
city: Atvidaberg
country: Sweden
facility: Research Site
city: Hollviken
country: Sweden
facility: Research Site
city: Limhamn
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Malmo
country: Sweden
facility: Research Site
city: Motala
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Uppsala
country: Sweden
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D Lund
name: Tomas Andersson, MD
role: STUDY_DIRECTOR
affiliation: Hannover Medical School
name: Tobias Welte, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nielsen R, Kankaanranta H, Bjermer L, Lange P, Arnetorp S, Hedegaard M, Stenling A, Mittmann N. Cost effectiveness of adding budesonide/formoterol to tiotropium in COPD in four Nordic countries. Respir Med. 2013 Nov;107(11):1709-21. doi: 10.1016/j.rmed.2013.06.007. Epub 2013 Jul 13.
citation: Mittmann N, Hernandez P, Mellstrom C, Brannman L, Welte T. Cost effectiveness of budesonide/formoterol added to tiotropium bromide versus placebo added to tiotropium bromide in patients with chronic obstructive pulmonary disease: Australian, Canadian and Swedish healthcare perspectives. Pharmacoeconomics. 2011 May;29(5):403-14. doi: 10.2165/11590380-000000000-00000.
citation: Partridge MR, Miravitlles M, Stahl E, Karlsson N, Svensson K, Welte T. Development and validation of the Capacity of Daily Living during the Morning questionnaire and the Global Chest Symptoms Questionnaire in COPD. Eur Respir J. 2010 Jul;36(1):96-104. doi: 10.1183/09031936.00123709. Epub 2009 Nov 6.
citation: Welte T, Miravitlles M, Hernandez P, Eriksson G, Peterson S, Polanowski T, Kessler R. Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2009 Oct 15;180(8):741-50. doi: 10.1164/rccm.200904-0492OC. Epub 2009 Jul 30.