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Evaluation of Efficacy and Safety of Symbicort® as an add-on Treatment to Spiriva® in Patients With Severe COPD.

Phase 4
Completed
Conditions
Chronic Obstructive Pulmonary Disease, COPD
Interventions
Registration Number
NCT00496470
Lead Sponsor
AstraZeneca
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
660
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Symbicort+TIOSymbicort (budesonide/formoterol turbuhaler 320/9ug)Symbicort Turbuhaler® (budesonide/formoterol) 320/9 mcg, one inhalation twice daily and Spiriva® (tiotropium) 18 mcg, one inhalation once daily
Spiriva® + Placebo TurbuhalerSpiriva (tiotropium bromide 18ug)Spiriva® (tiotropium) 18 mcg, one inhalation once daily and placebo Turbuhaler one inhalation once daily
Primary Outcome Measures
NameTimeMethod
Forced Expiratory Volume in 1 Second (FEV1) Pre-doseBaseline 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)

Secondary Outcome Measures
NameTimeMethod
Forced Expiratory Volume in 1 Second (FEV1) 5 Min Post-doseBaseline 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)

Forced Expiratory Volume in 1 Second (FEV1) 60 Min Post-doseBaseline 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)

Forced Vital Capacity (FVC) Pre-doseBaseline 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)

Forced Vital Capacity (FVC) 5 Minutes Post-doseBaseline 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)

Forced Vital Capacity (FVC) 60 Minutes Post-doseBaseline 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

Inspiratory Capacity (IC) Pre-doseBaseline 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)

Inspiratory Capacity (IC) 60 Minutes Post-doseBaseline 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)

St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) ScoreBaseline 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.

Morning Peak Expiratory Flow (PEF) Pre-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Evening Peak Expiratory Flow (PEF) Pre-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Morning Peak Expiratory Flow (PEF) 5 Min Post-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Morning Peak Expiratory Flow (PEF) 15 Min Post-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Morning Diary FEV1 Pre-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Evening Diary FEV1, Pre-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Morning Diary FEV1, 5 Minutes Post-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Morning Diary FEV1, 15 Minutes Post-doseBaseline to 12 weeks

Daily diary record. Change in average values from run-in to the full treatment period

Global Chest Symptoms Questionnaire (GCSQ) Score, Pre-doseBaseline 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.

GCSQ Score, 5 Minutes Post-doseBaseline 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.

GCSQ Score, 15 Minutes Post-doseBaseline 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.

Capacity of Day Living in the Morning (CDLM) ScoreBaseline 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.

Use of Rescue Medication, NightBaseline to 12 weeks

Daily diary record - Night, after evening measurement till morning. Change in average values from run-in to the full treatment period

Use of Rescue Medication, MorningBaseline to 12 weeks

Daily diary record - Morning, after morning measurement till midday. Change in average values from run-in to the full treatment period

Use of Rescue Medication, DayBaseline to 12 weeks

Daily diary record - Day, after morning measurement till evening. Change in average values from run-in to the full treatment period

Use of Rescue Medication, TotalBaseline 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

COPD Symptoms, Breathing ScoreBaseline 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

COPD Symptoms, Sleeping ScoreBaseline 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

COPD Symptoms, Chest ScoreBaseline 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

COPD Symptoms, Cough ScoreBaseline 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

Severe COPD Exacerbations12 weeks

Patients with worsening of COPD leading to treatment with systemic steroids (oral or parenteral), emergency room treatment or hospitalisation

Serum High-sensitivity C-reactive Protein (hsCRP)Baseline to 12 weeks

Ratio of treatment period mean to run-in value

Serum Interleukin 6 (IL-6)Baseline to 12 weeks

Ratio of treatment period mean to run-in value

Serum Interleukin 8 (IL-8)Baseline to 12 weeks

Ratio of treatment period mean to run-in value

Serum Monocyte Chemoattractant Protein-1 (MCP-1)Baseline to 12 weeks

Ratio of treatment period mean to run-in value

Serum Soluble Tumor Necrosis Factor-alpha (sTNF-alpha)Baseline to 12 weeks

Ratio of treatment period mean to run-in value

Serum Tumor Necrosis Factor-alpha (TNF-alpha)Baseline to 12 weeks

Ratio of treatment period mean to run-in value

Serum Vascular Cell Adhesion Molecule-1 (VCAM-1)Baseline to 12 weeks

Ratio of treatment period mean to run-in value

Trial Locations

Locations (1)

Research Site

🇸🇪

Uppsala, Sweden

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