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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00496470




Registration number
NCT00496470
Ethics application status
Date submitted
3/07/2007
Date registered
4/07/2007
Date last updated
9/11/2012

Titles & IDs
Public title
Evaluation of Efficacy and Safety of Symbicort® as an add-on Treatment to Spiriva® in Patients With Severe COPD.
Scientific 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
Secondary ID [1] 0 0
Eudract no:2006-006796-21
Secondary ID [2] 0 0
D5892C00015
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease, COPD 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Symbicort (budesonide/formoterol turbuhaler 320/9ug)
Treatment: Drugs - Spiriva (tiotropium bromide 18ug)

Active Comparator: Symbicort+TIO - Symbicort Turbuhaler® (budesonide/formoterol) 320/9 mcg, one inhalation twice daily and Spiriva® (tiotropium) 18 mcg, one inhalation once daily

Active Comparator: Spiriva® + Placebo Turbuhaler - Spiriva® (tiotropium) 18 mcg, one inhalation once daily and placebo Turbuhaler one inhalation once daily


Treatment: Drugs: Symbicort (budesonide/formoterol turbuhaler 320/9ug)
Symbicort (budesonide/formoterol turbuhaler 320/9ug)

Treatment: Drugs: Spiriva (tiotropium bromide 18ug)
Spiriva (tiotropium bromide 18ug)

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Forced Expiratory Volume in 1 Second (FEV1) Pre-dose - 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)
Timepoint [1] 0 0
Baseline to 12 weeks
Secondary outcome [1] 0 0
Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-dose - 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)
Timepoint [1] 0 0
Baseline to 12 weeks
Secondary outcome [2] 0 0
Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-dose - 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)
Timepoint [2] 0 0
Baseline to 12 weeks
Secondary outcome [3] 0 0
Forced Vital Capacity (FVC) Pre-dose - 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)
Timepoint [3] 0 0
Baseline to 12 weeks
Secondary outcome [4] 0 0
Forced Vital Capacity (FVC) 5 Minutes Post-dose - 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)
Timepoint [4] 0 0
Baseline to 12 weeks
Secondary outcome [5] 0 0
Forced Vital Capacity (FVC) 60 Minutes Post-dose - 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
Timepoint [5] 0 0
Baseline to 12 weeks
Secondary outcome [6] 0 0
Inspiratory Capacity (IC) Pre-dose - 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)
Timepoint [6] 0 0
Baseline to 12 weeks
Secondary outcome [7] 0 0
Inspiratory Capacity (IC) 60 Minutes Post-dose - 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)
Timepoint [7] 0 0
Baseline to 12 weeks
Secondary outcome [8] 0 0
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Score - 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.
Timepoint [8] 0 0
Baseline and 12 weeks
Secondary outcome [9] 0 0
Morning Peak Expiratory Flow (PEF) Pre-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [9] 0 0
Baseline to 12 weeks
Secondary outcome [10] 0 0
Evening Peak Expiratory Flow (PEF) Pre-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [10] 0 0
Baseline to 12 weeks
Secondary outcome [11] 0 0
Morning Peak Expiratory Flow (PEF) 5 Min Post-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [11] 0 0
Baseline to 12 weeks
Secondary outcome [12] 0 0
Morning Peak Expiratory Flow (PEF) 15 Min Post-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [12] 0 0
Baseline to 12 weeks
Secondary outcome [13] 0 0
Morning Diary FEV1 Pre-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [13] 0 0
Baseline to 12 weeks
Secondary outcome [14] 0 0
Evening Diary FEV1, Pre-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [14] 0 0
Baseline to 12 weeks
Secondary outcome [15] 0 0
Morning Diary FEV1, 5 Minutes Post-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [15] 0 0
Baseline to 12 weeks
Secondary outcome [16] 0 0
Morning Diary FEV1, 15 Minutes Post-dose - Daily diary record. Change in average values from run-in to the full treatment period
Timepoint [16] 0 0
Baseline to 12 weeks
Secondary outcome [17] 0 0
Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-dose - 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.
Timepoint [17] 0 0
Baseline to 12 weeks
Secondary outcome [18] 0 0
GCSQ Score, 5 Minutes Post-dose - 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.
Timepoint [18] 0 0
Baseline to 12 weeks
Secondary outcome [19] 0 0
GCSQ Score, 15 Minutes Post-dose - 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.
Timepoint [19] 0 0
Baseline to 12 weeks
Secondary outcome [20] 0 0
Capacity of Day Living in the Morning (CDLM) Score - 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.
Timepoint [20] 0 0
Baseline to 12 weeks
Secondary outcome [21] 0 0
Use of Rescue Medication, Night - Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period
Timepoint [21] 0 0
Baseline to 12 weeks
Secondary outcome [22] 0 0
Use of Rescue Medication, Morning - Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period
Timepoint [22] 0 0
Baseline to 12 weeks
Secondary outcome [23] 0 0
Use of Rescue Medication, Day - Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period
Timepoint [23] 0 0
Baseline to 12 weeks
Secondary outcome [24] 0 0
Use of Rescue Medication, Total - 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
Timepoint [24] 0 0
Baseline to 12 weeks
Secondary outcome [25] 0 0
COPD Symptoms, Breathing Score - 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
Timepoint [25] 0 0
Baseline to 12 weeks
Secondary outcome [26] 0 0
COPD Symptoms, Sleeping Score - 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
Timepoint [26] 0 0
Baseline to 12 weeks
Secondary outcome [27] 0 0
COPD Symptoms, Chest Score - 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
Timepoint [27] 0 0
Baseline to 12 weeks
Secondary outcome [28] 0 0
COPD Symptoms, Cough Score - 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
Timepoint [28] 0 0
Baseline to 12 weeks
Secondary outcome [29] 0 0
Severe COPD Exacerbations - Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation
Timepoint [29] 0 0
12 weeks
Secondary outcome [30] 0 0
Serum High-sensitivity C-reactive Protein (hsCRP) - Ratio of treatment period mean to run-in value
Timepoint [30] 0 0
Baseline to 12 weeks
Secondary outcome [31] 0 0
Serum Interleukin 6 (IL-6) - Ratio of treatment period mean to run-in value
Timepoint [31] 0 0
Baseline to 12 weeks
Secondary outcome [32] 0 0
Serum Interleukin 8 (IL-8) - Ratio of treatment period mean to run-in value
Timepoint [32] 0 0
Baseline to 12 weeks
Secondary outcome [33] 0 0
Serum Monocyte Chemoattractant Protein-1 (MCP-1) - Ratio of treatment period mean to run-in value
Timepoint [33] 0 0
Baseline to 12 weeks
Secondary outcome [34] 0 0
Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha) - Ratio of treatment period mean to run-in value
Timepoint [34] 0 0
Baseline to 12 weeks
Secondary outcome [35] 0 0
Serum Tumor Necrosis Factor-alpha (TNF-alpha) - Ratio of treatment period mean to run-in value
Timepoint [35] 0 0
Baseline to 12 weeks
Secondary outcome [36] 0 0
Serum Vascular Cell Adhesion Molecule-1 (VCAM-1) - Ratio of treatment period mean to run-in value
Timepoint [36] 0 0
Baseline to 12 weeks

Eligibility
Key inclusion criteria
- >=40 years of age, diagnosed COPD with symptoms >=2 years, pre-bronchodilatory FEV1
<=50% of PN
Minimum age
40 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Current respiratory tract disorder other than COPD, history of asthma or rhinitis,
significant or unstable cardiovascular disorder

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Research Site - Concord
Recruitment hospital [2] 0 0
Research Site - Sydney
Recruitment hospital [3] 0 0
Research Site - Auchenflower
Recruitment hospital [4] 0 0
Research Site - Carina Heights
Recruitment hospital [5] 0 0
Research Site - North Mackay
Recruitment hospital [6] 0 0
Research Site - Adelaide
Recruitment hospital [7] 0 0
Research Site - Daw Park
Recruitment hospital [8] 0 0
Research Site - Clayton
Recruitment hospital [9] 0 0
Research Site - Malvern
Recruitment hospital [10] 0 0
Research Site - Nedlands
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- Sydney
Recruitment postcode(s) [3] 0 0
- Auchenflower
Recruitment postcode(s) [4] 0 0
- Carina Heights
Recruitment postcode(s) [5] 0 0
- North Mackay
Recruitment postcode(s) [6] 0 0
- Adelaide
Recruitment postcode(s) [7] 0 0
- Daw Park
Recruitment postcode(s) [8] 0 0
- Clayton
Recruitment postcode(s) [9] 0 0
- Malvern
Recruitment postcode(s) [10] 0 0
- Nedlands
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
British Columbia
Country [3] 0 0
Canada
State/province [3] 0 0
Manitoba
Country [4] 0 0
Canada
State/province [4] 0 0
Newfoundland and Labrador
Country [5] 0 0
Canada
State/province [5] 0 0
Nova Scotia
Country [6] 0 0
Canada
State/province [6] 0 0
Ontario
Country [7] 0 0
Canada
State/province [7] 0 0
Quebec
Country [8] 0 0
Canada
State/province [8] 0 0
Saskatchewan
Country [9] 0 0
France
State/province [9] 0 0
Chamalieres
Country [10] 0 0
France
State/province [10] 0 0
Creil
Country [11] 0 0
France
State/province [11] 0 0
Ferolles Attilly
Country [12] 0 0
France
State/province [12] 0 0
Grasse
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
Marseille Cedex 06
Country [15] 0 0
France
State/province [15] 0 0
Metz
Country [16] 0 0
France
State/province [16] 0 0
Montpellier
Country [17] 0 0
France
State/province [17] 0 0
Perpignan
Country [18] 0 0
France
State/province [18] 0 0
Poitiers Cedex
Country [19] 0 0
France
State/province [19] 0 0
Selestat
Country [20] 0 0
France
State/province [20] 0 0
St Laurent Du Var
Country [21] 0 0
France
State/province [21] 0 0
Strasbourg Cedex
Country [22] 0 0
France
State/province [22] 0 0
Toulouse Cedex 9
Country [23] 0 0
Germany
State/province [23] 0 0
Berlin
Country [24] 0 0
Germany
State/province [24] 0 0
Gelsenkirchen
Country [25] 0 0
Germany
State/province [25] 0 0
Hagen
Country [26] 0 0
Germany
State/province [26] 0 0
Hannover
Country [27] 0 0
Germany
State/province [27] 0 0
Kassel
Country [28] 0 0
Germany
State/province [28] 0 0
Koblenz
Country [29] 0 0
Germany
State/province [29] 0 0
Leipzig
Country [30] 0 0
Germany
State/province [30] 0 0
Marburg
Country [31] 0 0
Germany
State/province [31] 0 0
Potsdam
Country [32] 0 0
Hungary
State/province [32] 0 0
Aszod
Country [33] 0 0
Hungary
State/province [33] 0 0
Baja
Country [34] 0 0
Hungary
State/province [34] 0 0
Balassagyarmat
Country [35] 0 0
Hungary
State/province [35] 0 0
Budapest
Country [36] 0 0
Hungary
State/province [36] 0 0
Cegled
Country [37] 0 0
Hungary
State/province [37] 0 0
Debrecen
Country [38] 0 0
Hungary
State/province [38] 0 0
Fuzesabony
Country [39] 0 0
Hungary
State/province [39] 0 0
Jaszbereny
Country [40] 0 0
Hungary
State/province [40] 0 0
Komlo
Country [41] 0 0
Hungary
State/province [41] 0 0
Nyiregyhaza
Country [42] 0 0
Hungary
State/province [42] 0 0
Torokbalint
Country [43] 0 0
Hungary
State/province [43] 0 0
Vásárosnamény
Country [44] 0 0
Poland
State/province [44] 0 0
Bydgoszcz
Country [45] 0 0
Poland
State/province [45] 0 0
Chrzanów
Country [46] 0 0
Poland
State/province [46] 0 0
Ilawa
Country [47] 0 0
Poland
State/province [47] 0 0
Krakow
Country [48] 0 0
Poland
State/province [48] 0 0
Lomza
Country [49] 0 0
Poland
State/province [49] 0 0
Piekary Slaskie
Country [50] 0 0
Poland
State/province [50] 0 0
Tarnow
Country [51] 0 0
Poland
State/province [51] 0 0
Turek
Country [52] 0 0
Poland
State/province [52] 0 0
Zawadzkie
Country [53] 0 0
Slovakia
State/province [53] 0 0
Kosice
Country [54] 0 0
Slovakia
State/province [54] 0 0
Liptovsky Hradok
Country [55] 0 0
Slovakia
State/province [55] 0 0
Lucenec
Country [56] 0 0
Slovakia
State/province [56] 0 0
Nove Mesto Nad Vahom
Country [57] 0 0
Slovakia
State/province [57] 0 0
Nove Zamky
Country [58] 0 0
Slovakia
State/province [58] 0 0
Piestany
Country [59] 0 0
Slovakia
State/province [59] 0 0
Poprad
Country [60] 0 0
Slovakia
State/province [60] 0 0
Povazska Bystrica
Country [61] 0 0
Slovakia
State/province [61] 0 0
Presov
Country [62] 0 0
Slovakia
State/province [62] 0 0
Prievidza
Country [63] 0 0
Slovakia
State/province [63] 0 0
Revuca
Country [64] 0 0
Slovakia
State/province [64] 0 0
Trnava
Country [65] 0 0
Slovakia
State/province [65] 0 0
Zilina
Country [66] 0 0
Spain
State/province [66] 0 0
Cataluna
Country [67] 0 0
Spain
State/province [67] 0 0
Comunidad de Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Comunidad Valenciana
Country [69] 0 0
Spain
State/province [69] 0 0
Galicia
Country [70] 0 0
Sweden
State/province [70] 0 0
Orebro Lan
Country [71] 0 0
Sweden
State/province [71] 0 0
Atvidaberg
Country [72] 0 0
Sweden
State/province [72] 0 0
Hollviken
Country [73] 0 0
Sweden
State/province [73] 0 0
Limhamn
Country [74] 0 0
Sweden
State/province [74] 0 0
Lund
Country [75] 0 0
Sweden
State/province [75] 0 0
Malmo
Country [76] 0 0
Sweden
State/province [76] 0 0
Motala
Country [77] 0 0
Sweden
State/province [77] 0 0
Stockholm
Country [78] 0 0
Sweden
State/province [78] 0 0
Uppsala

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00496470
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Tomas Andersson, MD
Address 0 0
AstraZeneca R&D Lund
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications