Differential Trough Effects of 'Triple Therapy' on Pulmonary Function in Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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Different medications are often used in combination for the condition COPD (chronic obstructive pulmonary disease). Some medicines act by opening the airways (bronchodilators) and some act as anti-inflammatories (steroids). More recently an approach of using a combination inhaler (containing a steroid and a long-acting bronchodilator) at the same time as a long acting bronchodilator of a different group of medicines (anti-cholinergics inhalers) has been used. This approach is sometimes called 'triple therapy'. Studies which have looked at these combinations usually use only standard blowing tests (spirometry) to test these medicines and focus on the effects of the medicines at their highest (peak) levels. It is some ways more relevant to study these medicines towards to end of the dose period (trough)- just before the next dose. This is when there is less medicine in the system, and differences in drug effects are more obvious. There are also more detailed breathing tests than spirometry which get a more detailed picture of the way the lungs respond to bronchodilator medicines. The investigators have studied 'triple therapy' in COPD, by measuring the effects at the end of the dosing interval (trough) using a range of detailed respiratory tests.

Official Title
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A Proof Of Concept Study To Evaluate Tiotropium as Add-on Therapy to Inhaled Budesonide/Formoterol Combination in COPD

Conditions
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COPD

Intervention / Treatment
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* Drug: Budesonide/formoterol and tiotropium
* Drug: Budesonide/formoterol and placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Current or ex-smokers aged over 50years FEV1/FVC ratio less than 0.7 FEV1 less than 60% predicted Exclusion Criteria: Diagnosis of asthma, ABPA or bronchiectasis Recent RTI or steroid use Inability to perform study procedures or to give informed consent Known sensitivity to trial medications

Ages Eligible for Study
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Minimum Age: 50 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Triple therapy<br>Symbicort and tiotropium | Drug: Budesonide/formoterol and tiotropium<br>* Symbicort 200/2, 2puff bid plus tiotropium 18mcg/day<br>|
| Placebo Comparator: Combination therapy<br>Symbicort and placebo | Drug: Budesonide/formoterol and placebo<br>* Symbicort 200/6 2puff bid and placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in trough FEV1 for tiotropium compared to placebo when added to formoterol/budesonide combination |  | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in IOS and bodyplethysmography at trough for tiotropium compared to placebo when added to formoterol/budesonide combination |  | 2 weeks | 
| Change in spirometry, IOS and Bodyplethysmography at trough for formoterol/budesonide compared to washed-out baseline |  | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD (chronic obstructive pulmonary disease)