- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00496470
Evaluation of Efficacy and Safety of Symbicort® as an add-on Treatment to Spiriva® in Patients With Severe COPD.
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 Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
New South Wales
-
Concord, New South Wales, Australia
- Research Site
-
Sydney, New South Wales, Australia
- Research Site
-
-
Queensland
-
Auchenflower, Queensland, Australia
- Research Site
-
Carina Heights, Queensland, Australia
- Research Site
-
North Mackay, Queensland, Australia
- Research Site
-
-
South Australia
-
Adelaide, South Australia, Australia
- Research Site
-
Daw Park, South Australia, Australia
- Research Site
-
-
Victoria
-
Clayton, Victoria, Australia
- Research Site
-
Malvern, Victoria, Australia
- Research Site
-
-
Western Australia
-
Nedlands, Western Australia, Australia
- Research Site
-
-
-
-
-
Quebec, Canada
- Research Site
-
-
Alberta
-
Calgary, Alberta, Canada
- Research Site
-
-
British Columbia
-
Vancouver, British Columbia, Canada
- Research Site
-
-
Manitoba
-
Winnipeg, Manitoba, Canada
- Research Site
-
-
Newfoundland and Labrador
-
St. John's, Newfoundland and Labrador, Canada
- Research Site
-
-
Nova Scotia
-
Halifax, Nova Scotia, Canada
- Research Site
-
-
Ontario
-
Mississauga, Ontario, Canada
- Research Site
-
Toronto, Ontario, Canada
- Research Site
-
-
Quebec
-
La Malbaie, Quebec, Canada
- Research Site
-
Trois-rivires, Quebec, Canada
- Research Site
-
-
Saskatchewan
-
Saskatoon, Saskatchewan, Canada
- Research Site
-
-
-
-
-
Chamalieres, France
- Research Site
-
Creil, France
- Research Site
-
Ferolles Attilly, France
- Research Site
-
Grasse, France
- Research Site
-
Lille, France
- Research Site
-
Marseille Cedex 06, France
- Research Site
-
Metz, France
- Research Site
-
Montpellier, France
- Research Site
-
Perpignan, France
- Research Site
-
Poitiers Cedex, France
- Research Site
-
Selestat, France
- Research Site
-
St Laurent Du Var, France
- Research Site
-
Strasbourg Cedex, France
- Research Site
-
Toulouse Cedex 9, France
- Research Site
-
-
-
-
-
Berlin, Germany
- Research Site
-
Gelsenkirchen, Germany
- Research Site
-
Hagen, Germany
- Research Site
-
Hannover, Germany
- Research Site
-
Kassel, Germany
- Research Site
-
Koblenz, Germany
- Research Site
-
Leipzig, Germany
- Research Site
-
Marburg, Germany
- Research Site
-
Potsdam, Germany
- Research Site
-
-
-
-
-
Aszod, Hungary
- Research Site
-
Baja, Hungary
- Research Site
-
Balassagyarmat, Hungary
- Research Site
-
Budapest, Hungary
- Research Site
-
Cegled, Hungary
- Research Site
-
Debrecen, Hungary
- Research Site
-
Fuzesabony, Hungary
- Research Site
-
Jaszbereny, Hungary
- Research Site
-
Komlo, Hungary
- Research Site
-
Nyiregyhaza, Hungary
- Research Site
-
Torokbalint, Hungary
- Research Site
-
Vásárosnamény, Hungary
- Research Site
-
-
-
-
-
Bydgoszcz, Poland
- Research Site
-
Chrzanów, Poland
- Research Site
-
Ilawa, Poland
- Research Site
-
Krakow, Poland
- Research Site
-
Lomza, Poland
- Research Site
-
Piekary Slaskie, Poland
- Research Site
-
Tarnow, Poland
- Research Site
-
Turek, Poland
- Research Site
-
Zawadzkie, Poland
- Research Site
-
-
-
-
-
Kosice, Slovakia
- Research Site
-
Liptovsky Hradok, Slovakia
- Research Site
-
Lucenec, Slovakia
- Research Site
-
Nove Mesto Nad Vahom, Slovakia
- Research Site
-
Nove Zamky, Slovakia
- Research Site
-
Piestany, Slovakia
- Research Site
-
Poprad, Slovakia
- Research Site
-
Povazska Bystrica, Slovakia
- Research Site
-
Presov, Slovakia
- Research Site
-
Prievidza, Slovakia
- Research Site
-
Revuca, Slovakia
- Research Site
-
Trnava, Slovakia
- Research Site
-
Zilina, Slovakia
- Research Site
-
-
-
-
Cataluna
-
Barcelona, Cataluna, Spain
- Research Site
-
Reus (tarragona), Cataluna, Spain
- Research Site
-
-
Comunidad Valenciana
-
Requena (valencia), Comunidad Valenciana, Spain
- Research Site
-
Valencia, Comunidad Valenciana, Spain
- Research Site
-
-
Comunidad de Madrid
-
Madrid, Comunidad de Madrid, Spain
- Research Site
-
-
Galicia
-
Pontevedra, Galicia, Spain
- Research Site
-
-
-
-
-
Atvidaberg, Sweden
- Research Site
-
Hollviken, Sweden
- Research Site
-
Limhamn, Sweden
- Research Site
-
Lund, Sweden
- Research Site
-
Malmo, Sweden
- Research Site
-
Motala, Sweden
- Research Site
-
Stockholm, Sweden
- Research Site
-
Uppsala, Sweden
- Research Site
-
-
Orebro Lan
-
Lindesberg, Orebro Lan, Sweden
- Research Site
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Symbicort+TIO
Symbicort Turbuhaler® (budesonide/formoterol) 320/9 mcg, one inhalation twice daily and Spiriva® (tiotropium) 18 mcg, one inhalation once daily
|
Symbicort (budesonide/formoterol turbuhaler 320/9ug)
|
Active Comparator: Spiriva® + Placebo Turbuhaler
Spiriva® (tiotropium) 18 mcg, one inhalation once daily and placebo Turbuhaler one inhalation once daily
|
Spiriva (tiotropium bromide 18ug)
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Forced Expiratory Volume in 1 Second (FEV1) Pre-dose
Time Frame: Baseline to 12 weeks
|
Change in the pre-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
|
Baseline to 12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose
Time Frame: Baseline to 12 weeks
|
Change in the 5 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
|
Baseline to 12 weeks
|
Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose
Time Frame: Baseline to 12 weeks
|
Change in the 60 min post-dose FEV1from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
|
Baseline to 12 weeks
|
Forced Vital Capacity (FVC) Pre-dose
Time Frame: Baseline to 12 weeks
|
Change in the pre-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
|
Baseline to 12 weeks
|
Forced Vital Capacity (FVC) 5 Minutes Post-dose
Time Frame: Baseline to 12 weeks
|
Change in the 5 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
|
Baseline to 12 weeks
|
Forced Vital Capacity (FVC) 60 Minutes Post-dose
Time Frame: Baseline to 12 weeks
|
Change in the 60 min post-dose FVC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12
|
Baseline to 12 weeks
|
Inspiratory Capacity (IC) Pre-dose
Time Frame: Baseline to 12 weeks
|
Change in the pre-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
|
Baseline to 12 weeks
|
Inspiratory Capacity (IC) 60 Minutes Post-dose
Time Frame: Baseline to 12 weeks
|
Change in the 60 min post-dose IC from baseline to week 12 (calculated as a mean using all available data of treatment period between week 1 and week 12)
|
Baseline to 12 weeks
|
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score
Time Frame: Baseline and 12 weeks
|
Change in total score from baseline (Visit 3) to end of treatment (Visit 6, or last available visit). SGRQ-C is a health related quality of life questionnaire consisting of 40 items divided into two components: 1) symptoms, 2) activity& impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. |
Baseline and 12 weeks
|
Morning Peak Expiratory Flow (PEF) Pre-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Evening Peak Expiratory Flow (PEF) Pre-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Morning Peak Expiratory Flow (PEF) 5 Min Post-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Morning Peak Expiratory Flow (PEF) 15 Min Post-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Morning Diary FEV1 Pre-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Evening Diary FEV1, Pre-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Morning Diary FEV1, 5 Minutes Post-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Morning Diary FEV1, 15 Minutes Post-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions. |
Baseline to 12 weeks
|
GCSQ Score, 5 Minutes Post-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions. |
Baseline to 12 weeks
|
GCSQ Score, 15 Minutes Post-dose
Time Frame: Baseline to 12 weeks
|
Daily diary record. Change in average values from run-in to the full treatment period. The GCSQ consisted of two questions that required the patient to rate shortness of breath and feelings of chest tightness. The patients recorded their response on a five-point Likert-type scale ranging from 0 (not at all) to 4 (extremely), the total score being calculated as the average score of the two questions. |
Baseline to 12 weeks
|
Capacity of Day Living in the Morning (CDLM) Score
Time Frame: Baseline to 12 weeks
|
Daily diary record. Change in average values from run-in to the full treatment period. The CDLM questionnaire is as a questionnaire to report on patient's ability to carry out each of six different morning activities (score ranging from 0 "not performed" to 1"performed") and rank the difficulty of performing each of those activities (score ranging from 0 "so difficult that the activity could not be carried out by the patient on their own" to 5 "activity was not at all difficult to carry out". Total score for each morning activity range from 0-6. Total score for whole CDLM questionnaire range from 0-36. |
Baseline to 12 weeks
|
Use of Rescue Medication, Night
Time Frame: Baseline to 12 weeks
|
Daily diary record - Night, after evening measurement till morning.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Use of Rescue Medication, Morning
Time Frame: Baseline to 12 weeks
|
Daily diary record - Morning, after morning measurement till midday.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Use of Rescue Medication, Day
Time Frame: Baseline to 12 weeks
|
Daily diary record - Day, after morning measurement till evening.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
Use of Rescue Medication, Total
Time Frame: Baseline to 12 weeks
|
Daily diary record - Total, 24 hours, during the night, and during the day.
Change in average values from run-in to the full treatment period
|
Baseline to 12 weeks
|
COPD Symptoms, Breathing Score
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period.
Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
|
Baseline to 12 weeks
|
COPD Symptoms, Sleeping Score
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period.
Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
|
Baseline to 12 weeks
|
COPD Symptoms, Chest Score
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period.
Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
|
Baseline to 12 weeks
|
COPD Symptoms, Cough Score
Time Frame: Baseline to 12 weeks
|
Daily diary record.
Change in average values from run-in to the full treatment period.
Symptom scale 0 - 4 (0) None (1) Mild (2) Moderate (3) Marked (4) Severe
|
Baseline to 12 weeks
|
Severe COPD Exacerbations
Time Frame: 12 weeks
|
Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation
|
12 weeks
|
Serum High-sensitivity C-reactive Protein (hsCRP)
Time Frame: Baseline to 12 weeks
|
Ratio of treatment period mean to run-in value
|
Baseline to 12 weeks
|
Serum Interleukin 6 (IL-6)
Time Frame: Baseline to 12 weeks
|
Ratio of treatment period mean to run-in value
|
Baseline to 12 weeks
|
Serum Interleukin 8 (IL-8)
Time Frame: Baseline to 12 weeks
|
Ratio of treatment period mean to run-in value
|
Baseline to 12 weeks
|
Serum Monocyte Chemoattractant Protein-1 (MCP-1)
Time Frame: Baseline to 12 weeks
|
Ratio of treatment period mean to run-in value
|
Baseline to 12 weeks
|
Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha)
Time Frame: Baseline to 12 weeks
|
Ratio of treatment period mean to run-in value
|
Baseline to 12 weeks
|
Serum Tumor Necrosis Factor-alpha (TNF-alpha)
Time Frame: Baseline to 12 weeks
|
Ratio of treatment period mean to run-in value
|
Baseline to 12 weeks
|
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)
Time Frame: Baseline to 12 weeks
|
Ratio of treatment period mean to run-in value
|
Baseline to 12 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tobias Welte, MD, Hannover Medical School
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Lung Diseases
- Lung Diseases, Obstructive
- Pulmonary Disease, Chronic Obstructive
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Parasympatholytics
- Autonomic Agents
- Peripheral Nervous System Agents
- Cholinergic Antagonists
- Cholinergic Agents
- Anti-Inflammatory Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Adrenergic Agonists
- Anticonvulsants
- Bronchodilator Agents
- Anti-Asthmatic Agents
- Respiratory System Agents
- Adrenergic beta-2 Receptor Agonists
- Adrenergic beta-Agonists
- Budesonide
- Tiotropium Bromide
- Bromides
- Formoterol Fumarate
- Budesonide, Formoterol Fumarate Drug Combination
Other Study ID Numbers
- D5892C00015
- Eudract no:2006-006796-21
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Chronic Obstructive Pulmonary Disease, COPD
-
University College, LondonUniversity of Cambridge; National Institute for Health Research, United Kingdom and other collaboratorsUnknownChronic Obstructive Pulmonary Disease (COPD).United Kingdom
-
Virginia Commonwealth UniversityFisher and Paykel HealthcareCompletedChronic Obstructive Pulmonary Disease(COPD)United States
-
Reham Mohammed ElmorshedyCompletedChronic Obstructive Pulmonary Disease(COPD)Egypt
-
AstraZenecaCompletedChronic Obstructive Pulmonary Disease (COPD).United Kingdom
-
Medtronic BRCUnknownCOPD | COPD Exacerbation
-
Beaumont HospitalAerogenCompletedChronic Obstructive Pulmonary Disease | COPD | COPD Exacerbation | Copd Exacerbation AcuteIreland
-
Chiesi Farmaceutici S.p.A.CompletedModerate to Severe Chronic Obstructive Pulmonary Disease (COPD)Bulgaria, Germany, Hungary, Poland, Russian Federation, United Kingdom
-
Chiesi Farmaceutici S.p.A.CompletedChronic Obstructive Pulmonary Disease (COPD) | COPDUnited Kingdom
-
Rigshospitalet, DenmarkUnknown
-
Elpen Pharmaceutical Co. Inc.Completed
Clinical Trials on Symbicort (budesonide/formoterol turbuhaler 320/9ug)
-
Orion Corporation, Orion PharmaCompleted
-
Orion Corporation, Orion PharmaCompleted
-
AstraZenecaCompletedChronic Obstructive Pulmonary DiseaseKorea, Republic of, Poland, Russian Federation, Vietnam, Philippines, Ukraine, Japan, Taiwan, India
-
AstraZenecaCompleted
-
Orion Corporation, Orion PharmaCompleted
-
AstraZenecaCompletedChronic Obstructive Pulmonary Disease (COPD)Germany
-
AstraZenecaCompletedBronchial AsthmaBulgaria, Czech Republic, Poland, Hungary
-
Pearl Therapeutics, Inc.Completed
-
AstraZenecaRecruitingAsthmaUnited States, Canada, Italy, Japan, Vietnam, Spain, Germany, Malaysia
-
Meir Medical CenterUnknown