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NCT Number: NCT03104634

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

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.

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Key information

Conditions

Smoking Behavior

Age range

45 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

McGill University Health Centre Research Institute

Montreal, Quebec, H4A 3J1, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Aclidinium bromide/formoterol fumarate dihydrate

Drug

Cross-over design with washout interval. Randomized order of active and placebo arm

Other names: DUAKLIR™ GENUAIR®

Placebo

Drug

Placebo and delivery device matched to active intervention

Primary outcomes

  1. Inspiratory pleural pressures at rest and throughout incremental exercise (cmH2O)

    Time frame: 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 outcomes

  1. Resting and exercise-induced changes in plasma natriuretic peptide concentrations (plasma concentration)

    Time frame: 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).

  2. Resting and dynamic lung volumes (end-inspiratory/end-expiratory lung volume)

    Time frame: After 7-days of active or placebo drug

    Static and operating lung volumes

  3. Effect modification by gender (self-reported).

    Time frame: After 7-days of active or placebo drug

    Interaction term added to regression model for gender.

  4. Effect modification by smoking status (self-reported).

    Time frame: After 7-days of active or placebo drug

    Interaction term added to regression model for smoking status.

  5. Effect modification by hypertension status (Joint National Committee criteria).

    Time frame: After 7-days of active or placebo drug

    Interaction term added to regression model for hypertension status.

  6. Effect modification by hyperinflation severity (Residual lung volume).

    Time frame: After 7-days of active or placebo drug

    Interaction term added to regression model for hyperinflation severity.

  7. Effect modification by spirometric chronic obstructive pulmonary disease (COPD) status (forced expired volume in 1 second-to-forced vital capacity ratio below 0.7).

    Time frame: After 7-days of active or placebo drug

    Interaction term added to regression model for spirometric COPD status.

Sponsors and collaborators

Lead sponsor

McGill University Health Centre/Research Institute of the McGill University Health Centre

Other

Registry information

Official study title

The Effects of Inhaled Aclidinium Bromide/Formoterol Fumarate on Inspiratory Pleural Pressures in Smokers: a Randomized, Double-blind, Placebo-controlled, Cross-over Trial

Important dates

Study start
2017
Primary completion
2018
Study completion
2019
First posted
Apr 7, 2017
Registry last updated
Apr 8, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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