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

McGill University

Status and phase: Completed; Phase 3

Conditions: Smoking

Treatments: Drug: Placebo; Drug: Aclidinium bromide/formoterol fumarate dihydrate

Study type: Interventional

Funder types: Other

Identifiers

NCT03104634

2017-2748

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 45 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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43 participants in 2 patient groups, including a placebo group

Active arm

Experimental group

Description:

Aclidinium bromide/formoterol fumarate dihydrate 400 mcg/12 mcg Twice daily (once in the morning, once in the evening) 7-days

Treatment:

Drug: Aclidinium bromide/formoterol fumarate dihydrate

Placebo arm

Placebo Comparator group

Description:

Placebo Twice daily (once in the morning, once in the evening) 7-days

Treatment:

Drug: Placebo