The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers
Study Details
Study Description
Brief Summary
This short-term study aims to prove the potential cardio-protective physiological effect of inhaled aclidinium bromide/formoterol fumarate on inspiratory pleural pressures.
Smoking is associated with gas-trapping (hyperinflation), even in the absence of chronic obstructive pulmonary disease. Breathing in the presence of gas-trapping requires large negative inspiratory pleural pressures, which are transmitted to the surface of the heart and increase cardiac wall stress.
Inhaled aclidinium bromide and formoterol fumarate has been shown to reduce gas-trapping, but the impact on inspiratory pleural pressures and biomarkers of cardiac stress in smokers is unknown.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Active arm Aclidinium bromide/formoterol fumarate dihydrate 400 mcg/12 mcg Twice daily (once in the morning, once in the evening) 7-days |
Drug: Aclidinium bromide/formoterol fumarate dihydrate
Cross-over design with washout interval. Randomized order of active and placebo arm
Other Names:
|
| Placebo Comparator: Placebo arm Placebo Twice daily (once in the morning, once in the evening) 7-days |
Drug: Placebo
Placebo and delivery device matched to active intervention
|
Outcome Measures
Primary Outcome Measures
- Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O) [After 7-days of active or placebo drug]
Mean difference in inspiratory pleural pressure measured by esophageal manometry at rest and throughout incremental exercise
Secondary Outcome Measures
- Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration) [After 7-days of active or placebo drug]
Mean difference in atrial natriuretic peptide (exercise induced-changes) and n-terminal pro-B-type natriuretic peptide (resting).
- Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume) [After 7-days of active or placebo drug]
Static and operating lung volumes
- Effect modification by gender (self-reported). [After 7-days of active or placebo drug]
Interaction term added to regression model for gender.
- Effect modification by smoking status (self-reported). [After 7-days of active or placebo drug]
Interaction term added to regression model for smoking status.
- Effect modification by hypertension status (Joint National Committee criteria). [After 7-days of active or placebo drug]
Interaction term added to regression model for hypertension status.
- Effect modification by hyperinflation severity (Residual lung volume). [After 7-days of active or placebo drug]
Interaction term added to regression model for hyperinflation severity.
- Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7). [After 7-days of active or placebo drug]
Interaction term added to regression model for spirometric COPD status.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Current and former smokers with ≥20 pack-years of smoking history
-
Gas-trapping (residual volume >110% predicted)
Exclusion Criteria:
Physician-diagnosis of chronic obstructive pulmonary disease in the past 1 year and regular use of long-acting antimuscarinic (LAMA) and/or long-acting beta-agonist (LABA) (i.e., at least 30 consecutive days)
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Physician-diagnosis of asthma in the past 5 years
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Regular inhaled corticosteroid (ICS) use in the past 5 years (i.e., at least 30 consecutive days)
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Physician-diagnosis of other lung diseases (sarcoidosis, tuberculosis, cystic fibrosis, pulmonary fibrosis, lung cancer), or long-term oxygen therapy
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Respiratory tract infection within 4-weeks
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Physician-diagnosis of arrhythmia, or significant valvular disease.
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Physician-diagnosis of myocardial infarction, unstable angina or heart failure requiring unscheduled outpatient or emergency department visit within 6-months.
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Arrhythmia or prolonged corrected QT (QTc) on electrocardiogram.
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Inability to use study inhaler
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Glaucoma
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Benign prostatic hypertrophy
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Pregnancy
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Allergy to the study treatment, salbutamol, lidocaine, or severe milk protein allergy (note: lactose intolerance is not an exclusion criteria)
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Contraindications to anti-cholinergic, beta-agonist, or cardiopulmonary exercise testing with manometry
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Inability to provide written informed consent
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | McGill University Health Centre Research Institute | Montreal | Quebec | Canada | H4A 3J1 |
Sponsors and Collaborators
- McGill University Health Centre/Research Institute of the McGill University Health Centre
Investigators
- Principal Investigator: B M Smith, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2017-2748