Predictor for an Additional Benefit of Inhaled Corticosteroid in Patients Treated With Tiotropium for COPD

Study Overview
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Brief Summary
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Study purpose is to evaluate if subjects with chronic obstructive pulmonary disease (COPD) are more likely to be responsive to additional inhaled corticosteroids if they have a positive response to hyperosmolar challenge with mannitol than if their response is negative.

Detailed Description
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In patients with chronic obstructive pulmonary disease (COPD), the treatment with inhaled corticosteroids (ICS) is controversial. Preliminary results of our recent pilot study in 30 COPD patients showed for the first time, that ICS response mey be predicted by a bronchoprovocation challenge test with mannitol. However, this finding needs to be proven in a placebo-controlled trial. For this cohort study, 100 corticosteroid-naive, non reversible (FEV1) patients with COPD will be recruited. Spirometry before and after bronchodilation will be measured at study entry and at four weeks run-in (only tiotropium) and at three month of treatment with tiotropium and ICS or placebo. Quality of life (St. George Respiratory Quality of Life Questionnaire) and exacerbation rate of COPD will be assessed. Measurement of exhaled nitric oxide and mannitol challenge will be performed at study entry and at 1 and 4 month. Primary endpoint will be improvement in FEV1 in each group (positive and negative mannitol challenge) after 3 months follow up. Secondary endpoints will be the difference in dose-response-curve in the mannitol challenge, exacerbation rate and change in quality of life after three month follow-up.

Official Title
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Predictor for an Additional Benefit of Inhaled Corticosteroid in Patients Treated With Tiotropium for Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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COPD

Intervention / Treatment
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* Drug: Budesonide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: FEV1/FVC < 70% FEV1 % predicted > 60% Exclusion Criteria: Other major disease Asthma Currently taking inhaled corticosteroids oral corticosteroids in the last 3 month significant cardiovascular disease pregnancy/breast feeding current use of salmeterol or other long acting bronchodilator

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Budesonide<br> | Drug: Budesonide<br>* After 4 weeks of inhalative therapy with tiotropium (all patients), patient get randomized to receive either inhalative budesonide (1600ug per day or placebo<br>* Other names: Miflonide;|
| Placebo Comparator: Placebo<br> | Drug: Budesonide<br>* After 4 weeks of inhalative therapy with tiotropium (all patients), patient get randomized to receive either inhalative budesonide (1600ug per day or placebo<br>* Other names: Miflonide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Lung Function (FEV1) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Proportion Who Complete Follow-up Without Developing an Exacerbation |  | 12 weeks | 
| Change in Quality of Life | St. George Respiratory Questionnaire (SGRQ). Disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores are calculated for three domains: Part I (Symptoms): several scales; Part II (Activity and Impacts): dichotomous (true/false) except last question (4-point Likert scale) Scores range from 0 to 100, with higher scores indicating more limitations. Unit of Measure = Units on a scale A minimum change in score of 4 units was established as clinically relevant after patient and clinician testing. Based on empirical data and interviews with patients, a mean change score of 4 units is associated with slightly efficacious treatment, 8 units for moderately efficacious change and 12 units for very efficacious treatment. The higher the change in units, the better the treatment. | 12 weeks, baseline to 3 months follow-up | 
| Change in logRDR Mannitol |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, Inhaled corticosteroids, mannitol