Bronchodilators for Chronic Obstructive Pulmonary Disease

(SOUND Trial)

Recruiting in Palo Alto (17 mi)

Overseen by J Alberto Neder, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: Dr. J. Alberto Neder

Disqualifiers: Asthma, Pulmonary hypertension, Congestive heart failure, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Bronchodilators are medications that open the bronchi to help patients with COPD to breathe better. It is still not known exactly how this effect improves shortness of breath in people with COPD. The goal of this clinical trial is to determine whether bronchodilators lower resistance in the smallest airways in the lungs, and whether this will improve the feeling of breathlessness in these patients. The main questions the investigators attempt to answer are: * In patients with COPD, does treatment with a short-acting bronchodilator improve small airway resistance during exercise? * In patients with COPD, does acute treatment with short-acting bronchodilator improve breathlessness and exercise endurance? The investigators will compare short-acting bronchodilators to placebo (a substance that contains no drug) to see if the bronchodilator medications improve small airway resistance and breathlessness during exercise. Participants will: * Visit the research laboratory 3 visits to complete tests of lung function and exercise * Complete 2 identical visits (Visit 2 and 3), one in which the participant receives bronchodilator and one in which the participant receives placebo.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug bronchodilators for chronic obstructive pulmonary disease (COPD)?

Research shows that bronchodilators, like salmeterol and ipratropium, can improve lung function in people with COPD when used over a long period. These drugs are central to managing symptoms and have been shown to improve clinical outcomes compared to a placebo. ^{1 2 3 4 5}

What safety data exists for bronchodilators used in COPD treatment?

Bronchodilators are generally considered safe at recommended doses, but they can cause adverse reactions, especially affecting the skin. Long-acting muscarinic antagonists (LAMAs) are safe at recommended doses, but may cause side effects in the heart, digestive, and urinary systems if used at higher doses. ^{6 7 8 9 10}

How do bronchodilators differ from other COPD drugs?

Bronchodilators are unique because they directly relax the muscles around the airways, making it easier to breathe. They are available in short-acting forms for quick relief and long-acting forms for ongoing management, often used in combination with other medications to simplify treatment and improve adherence. ^{6 7 11 12 13}

Research Team

J Alberto Neder, MD, PhD

Principal Investigator

Kingston Health Sciences Centre

Eligibility Criteria

This trial is for individuals with Chronic Obstructive Pulmonary Disease (COPD). Participants will need to visit the research lab three times for lung function and exercise tests. They must be able to perform these activities and not have any other health conditions that could interfere with the study.

Inclusion Criteria

My condition has been stable for the last 6 weeks.

I am 40 years old or older.

Forced expiratory volume in 1 second (FEV1)/ forced vital capacity < lower limit of normal

Exclusion Criteria

Use of daytime oxygen or exercise induced O2 desaturation to < 80% on room air

I have a condition that makes it hard to breathe or exercise.

I do not have major heart or lung diseases except for COPD.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants undergo lung function and exercise tests with bronchodilator and placebo in a crossover design

2-3 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Treatment Details

Interventions

• Bronchodilators (Bronchodilator)

Trial Overview The trial is testing if short-acting bronchodilators can reduce resistance in small airways and ease breathlessness during exercise, compared to a placebo. Patients will receive both treatments on separate visits to see which one works better.

Participant Groups

Group I: Bronchodilator Active Control 1 Intervention

Participants will receive a combination short-acting bronchodilator (Salbutamol sulphate (2.5 mg) + ipratropium bromide (0.5 mg)) via nebulizer.

Group II: Placebo Placebo Group 1 Intervention

Participants will receive normal saline via nebulizer.

Who Is Running the Clinical Trial?

Dr. J. Alberto Neder

Lead Sponsor

Trials

1

Recruited

30+

Dr. J. Alberto Neder

Lead Sponsor

Trials

1

Recruited

30+

Findings from Research

In a study of 63 patients with moderate to severe COPD, treatment with salmeterol significantly improved morning peak expiratory flow (PEF) and reduced respiratory symptoms compared to placebo, indicating its efficacy as a long-term treatment option.

Patients reported better overall satisfaction with salmeterol treatment, and it led to less reliance on rescue medication, suggesting that long-acting beta agonists can enhance functional status even in cases of nonreversible airway obstruction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary disease: a single centre randomised, double blind, placebo controlled, crossover study. Ulrik, CS.[2019]

Aclidinium bromide significantly reduced the incidence of exacerbation-related hospitalizations and improved quality of life in patients with stable COPD, based on a meta-analysis of 7 studies involving 7001 patients.

The treatment also enhanced pulmonary function and alleviated symptoms of dyspnea without increasing the risk of serious adverse events or mortality, indicating its safety and efficacy as a bronchodilator for COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an Aclidinium Bromide Treatment for 12 Weeks or Longer in Patients with Moderate-To-Severe COPD: A Meta-Analysis. Zou, Y., Xiao, J., Yang, DH., et al.[2018]

In a 7-year study analyzing adverse drug reactions (ADRs) from bronchodilator therapy in two hospitals in Italy, bronchodilators were linked to 18.5% of ADR episodes, with theophylline being the most frequently implicated drug (53.4%).

The study found that skin reactions were the most common type of ADR (47.7%), and in 86% of cases, stopping the bronchodilator led to recovery, highlighting the importance of monitoring for ADRs in hospitalized patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective analysis of adverse drug reactions to bronchodilators observed in two pulmonary divisions of Catanzaro, Italy. Gallelli, L., Ferreri, G., Colosimo, M., et al.[2019]

Bronchodilators are essential for treating chronic obstructive pulmonary disease (COPD) by improving lung function, reducing symptoms, and enhancing quality of life, with ongoing developments focusing on safety and once-daily dosing.

Research is also exploring novel pharmacologic targets, such as EP4 receptor agonists and selective PDE inhibitors, which could lead to new treatment options and combination therapies for COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New bronchodilators. Mak, G., Hanania, NA.[2022]

Umeclidinium, a long-acting muscarinic receptor antagonist (LAMA), has been shown to be safe even at twice the recommended dosage in a study involving a Japanese population with chronic obstructive pulmonary disease (COPD).

Despite its safety profile, LAMAs like umeclidinium can potentially cause adverse effects due to muscarinic receptors being present in other organs such as the heart and digestive system, highlighting the need for further studies to assess their risk profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of long acting muscarinic antagonists: are all these drugs always and equally safe? Melani, AS., Sestini, P.[2018]

Inhaled bronchodilators are essential for managing chronic obstructive pulmonary disease (COPD), with short-acting types providing immediate symptom relief and long-acting types recommended for ongoing maintenance in more severe cases.

Combining different classes of long-acting bronchodilators may enhance symptom control for patients not adequately managed by a single medication, with ongoing developments in combination inhalers aimed at improving efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future of chronic obstructive pulmonary disease management. D'Urzo, A., Vogelmeier, C.[2012]

A systematic review of 51 randomized controlled trials involving 37,225 COPD patients demonstrated that long-acting bronchodilators significantly improve Health Related Quality of Life (HRQoL) and Health Status (HS) in 93% of the studies analyzed.

While the improvements in HRQoL/HS were statistically significant, only 70.6% of studies achieved the Minimal Important Difference (MID) from baseline, indicating that while effective, the clinical significance of the improvements varied among studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting bronchodilators improve health related quality of life in patients with COPD. Braido, F., Baiardini, I., Cazzola, M., et al.[2013]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy of inhaled salmeterol in the management of smokers with chronic obstructive pulmonary disease: a single centre randomised, double blind, placebo controlled, crossover study. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Extended therapy with ipratropium is associated with improved lung function in patients with COPD. A retrospective analysis of data from seven clinical trials. [2019]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Onset of action of formoterol versus salmeterol via dry powder inhalers in moderate chronic obstructive pulmonary disease: a randomized, placebo-controlled, double-blind, crossover study. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Comparison of indacaterol with tiotropium or twice-daily long-acting β -agonists for stable COPD: a systematic review. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Megatrials for bronchodilators in chronic obstructive pulmonary disease (COPD) treatment: time to reflect. [2013]

6. United States pubmed.ncbi.nlm.nih.gov

Pharmacology and therapeutics of bronchodilators. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of an Aclidinium Bromide Treatment for 12 Weeks or Longer in Patients with Moderate-To-Severe COPD: A Meta-Analysis. [2018]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Retrospective analysis of adverse drug reactions to bronchodilators observed in two pulmonary divisions of Catanzaro, Italy. [2019]

9. England pubmed.ncbi.nlm.nih.gov

New bronchodilators. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Safety of long acting muscarinic antagonists: are all these drugs always and equally safe? [2018]

11. England pubmed.ncbi.nlm.nih.gov

Future of chronic obstructive pulmonary disease management. [2012]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Readmission Risk in Chronic Obstructive Pulmonary Disease Patients: Comparative Study of Nebulized &#946;2-Agonists. [2020]

13. England pubmed.ncbi.nlm.nih.gov

Long-acting bronchodilators improve health related quality of life in patients with COPD. [2013]