Clinical trial NCT03104634: The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers
Official title: The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers: a Randomized, Double-blind, Placebo-controlled, Cross-over Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Smoking
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
First posted: 2017-04-07
Enrollment: 43
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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)

* Physician-diagnosis of asthma in the past 5 years
* Regular inhaled corticosteroid (ICS) use in the past 5 years (i.e., at least 30 consecutive days)
* Physician-diagnosis of other lung diseases (sarcoidosis, tuberculosis, cystic fibrosis, pulmonary fibrosis, lung cancer), or long-term oxygen therapy
* Respiratory tract infection within 4-weeks
* Physician-diagnosis of arrhythmia, or significant valvular disease.
* Physician-diagnosis of myocardial infarction, unstable angina or heart failure requiring unscheduled outpatient or emergency department visit within 6-months.
* Arrhythmia or prolonged corrected QT (QTc) on electrocardiogram.
* Inability to use study inhaler
* Glaucoma
* Benign prostatic hypertrophy
* Pregnancy
* Allergy to the study treatment, salbutamol, lidocaine, or severe milk protein allergy (note: lactose intolerance is not an exclusion criteria)
* Contraindications to anti-cholinergic, beta-agonist, or cardiopulmonary exercise testing with manometry
* Inability to provide written informed consent

Primary outcomes:
measure: Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O)
timeFrame: After 7-days of active or placebo drug
Secondary outcomes:
measure: Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration)
timeFrame: After 7-days of active or placebo drug
measure: Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume)
timeFrame: After 7-days of active or placebo drug
measure: Effect modification by gender (self-reported).
timeFrame: After 7-days of active or placebo drug
measure: Effect modification by smoking status (self-reported).
timeFrame: After 7-days of active or placebo drug
measure: Effect modification by hypertension status (Joint National Committee criteria).
timeFrame: After 7-days of active or placebo drug
measure: Effect modification by hyperinflation severity (Residual lung volume).
timeFrame: After 7-days of active or placebo drug
measure: Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7).
timeFrame: After 7-days of active or placebo drug
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: McGill University Health Centre Research Institute
state: Quebec
Study officials:
affiliation: McGill University Health Centre/Research Institute of the McGill University Health Centre
name: B M Smith, MD
role: PRINCIPAL_INVESTIGATOR
References: