Symbicort in Airway Predominant Chronic Obstructive Pulmonary Disease (COPD)

Study Overview
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Brief Summary
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The main objective of the study is to see if using anti-inflammatory to patients with airway disease chronic obstructive pulmonary disease (COPD) phenotype will be more effective than using these treatments in patients with loss of lung tissue. Symbicort plus ipratropium/albuterol will be used for 12 weeks in an open-label study in subjects with airway predominant COPD.

Detailed Description
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Subjects from the COPDGene study who have airway-predominant COPD on chest CT scan will be enrolled; a total of 40 subjects is planned. Subjects will all have background ipratropium-albuterol administered four times daily. Subjects will be randomized to receive budesonide (180 ug twice daily) or formoterol-budesonide (160/4.5 ug twice daily) for 12 weeks. The main objective is to explore novel outcomes: blood biomarkers and chest CT scan. Outcomes include lung function, walk distance, respiratory disease-specific health status, and expiratory chest CT scan gas trapping as an exploratory outcome. The primary outcome measure will be FEV1 pre-bronchodilator 12 hours after the last dose of study medication at the end of 12 weeks of treatment. FEV1 will be measured in the morning 6 hours after the last dose of ipratropium/albuterol and 12 hours after the last dose of budesonide and budesonide/formoterol

Official Title
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COPDGene Ancillary Proposal: Symbicort Intervention in Airway Predominant

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Drug: Budesonide
* Drug: budesonide/formoterol
* Drug: Ipratropium/albuterol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COPD GOLD Stage 2 and 3 (post-bronchodilator FEV1 35-80% predicted and FEV1/FVC <0.7 at the time of enrollment in COPDGene) by spirometry. Less than 15% of the lung <-950 Hounsfield Units on COPDGene high-resolution inspiratoryChest CT scan (i.e. no evidence of significant emphysema) Greater than 10% gas trapping on COPDGene expiratory CT scan (i.e. evidence of small airway disease). No history of recent use (within the pat 8 weeks) of an inhaled or systemic corticosteroid. Body weight <100 kg (low dose CT scans in subject with increased boyd weight can not be reliably analyzed). Exclusion Criteria: Exacerbation of COPD or other respiratory illness requiring antibiotics within the past 8 weeks. Previous adverse reaction to inhaled steroids, long-acting beta agonists, or long-acting anticholinergic medications. Symptomatic, untreated benign prostate hypertrophy. Allergy to peanuts. Glaucoma

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ipratropium/albuterol<br>1 puff 4 times daily | Drug: Ipratropium/albuterol<br>* Inhaled ipratropium/albuterol combination 2 puffs four times daily<br>* Other names: Combivent®;|
| Experimental: Budesonide<br>budesonide 180 ug 2 puffs 4 times daily + ipratropium/albuterol 1 puffs four times daily | Drug: Budesonide<br>* Inhaled budesonide twice daily plus inhaled ipratropium/albuterol combination four times daily and every 4 hours as needed<br>* Other names: Pulmicort Flexhaler®;Drug: Ipratropium/albuterol<br>* Inhaled ipratropium/albuterol combination 2 puffs four times daily<br>* Other names: Combivent®;|
| Experimental: budesonide/formoterol<br>budesonide/formoterol 160/4.5 ug 2 puffs 4 times daily + ipratropium/albuterol 1 puffs four times daily | Drug: budesonide/formoterol<br>* Inhaled budesonide/formoterol (160/4.5 mcg Symbicort®) 2 puffs twice daily plus inhaled ipratropium/albuterol (Combivent®) 1 puff four times daily<br>* Other names: Symbicort®;Drug: Ipratropium/albuterol<br>* Inhaled ipratropium/albuterol combination 2 puffs four times daily<br>* Other names: Combivent®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced expiratory volume in 1 second (FEV1) pre-bronchodilator | FEV1 will be measured in the morning 6 hours after the last dose of ipratropium/albuterol and 12 hours after the last dose budesonide and budesonide/formoterol | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health Status | Administer St. George's Respiratory Questionnaire at randomization and 12 weeks. | 12 weeks | 
| Dyspnea | Evaluated by the Modified Medical Research Council Dyspnea Scale at randomization and week 12. | 12 weeks | 
| Six minute walk distance | Evaluate six minute walk distance at randomization and 12 weeks | 12 weeks | 
| Forced vital capacity (FVC) pre-bronchodilator |  | 12 weeks | 
| Post-bronchodilator FEV1 |  | 12 weeks | 
| Patient-reported exacerbations |  | 12 weeks | 
| Patient reported adverse events |  | 12 weeks | 
| Post-bronchodilator FVC |  | 12 weeks | 
| CT scan gas trapping |  | Before and 12 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD