The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers

Smoking Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03104634
• Other study ID #: 2017-2748
• Status: Completed
• Phase: Phase 3
• Start date: May 1, 2017
• Est. completion date: February 1, 2019

Study information

• Verified date: April 2019
• Source: McGill University Health Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 43
• Est. completion date: February 1, 2019
• Est. primary completion date: December 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Smoking

Intervention

Drug:
• Aclidinium bromide/formoterol fumarate dihydrate
Cross-over design with washout interval. Randomized order of active and placebo arm
• Placebo
Placebo and delivery device matched to active intervention

Locations

Country	Name	City	State
Canada	McGill University Health Centre Research Institute	Montreal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
McGill University Health Center

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O)	Mean difference in inspiratory pleural pressure measured by esophageal manometry at rest and throughout incremental exercise	After 7-days of active or placebo drug
Secondary	Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration)	Mean difference in atrial natriuretic peptide (exercise induced-changes) and n-terminal pro-B-type natriuretic peptide (resting).	After 7-days of active or placebo drug
Secondary	Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume)	Static and operating lung volumes	After 7-days of active or placebo drug
Secondary	Effect modification by gender (self-reported).	Interaction term added to regression model for gender.	After 7-days of active or placebo drug
Secondary	Effect modification by smoking status (self-reported).	Interaction term added to regression model for smoking status.	After 7-days of active or placebo drug
Secondary	Effect modification by hypertension status (Joint National Committee criteria).	Interaction term added to regression model for hypertension status.	After 7-days of active or placebo drug
Secondary	Effect modification by hyperinflation severity (Residual lung volume).	Interaction term added to regression model for hyperinflation severity.	After 7-days of active or placebo drug
Secondary	Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7).	Interaction term added to regression model for spirometric COPD status.	After 7-days of active or placebo drug