Bronchodilators for Chronic Obstructive Pulmonary Disease

(SOUND Trial)

Overseen By J Alberto Neder Serafini, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Dr. J. Alberto Neder

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 3

Duration: 2-3 weeks

25 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if short-acting bronchodilators (medications that open the airways in the lungs) can help people with chronic obstructive pulmonary disease (COPD) breathe easier during exercise by reducing resistance in the small airways. Researchers will administer either the bronchodilator or a placebo (a fake treatment) to compare their effects on breathlessness and exercise endurance. The trial seeks current or former smokers with COPD who experience shortness of breath during daily activities. Participants will visit a lab for lung and exercise tests. As a Phase 4 trial, this research involves an FDA-approved treatment, aiming to understand how it can benefit more patients with COPD.

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 is the safety track record for bronchodilators?

Research has shown that the combination of salbutamol (also known as albuterol) and ipratropium is generally safe for people with COPD. In previous studies, patients tolerated this combination well.

One study lasting 29 days with 357 patients showed that this treatment improved lung function without causing serious side effects. Another study found that using the combination four times a day for 85 days led to noticeable improvements in breathing for most patients.

Although these studies did not report major side effects, it is always important to monitor how the body reacts to any medication. Clinical trial participants are closely monitored for any side effects, ensuring that safety remains a top priority. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike the standard treatments for Chronic Obstructive Pulmonary Disease (COPD), which often involve long-acting bronchodilators and inhaled corticosteroids, this study treatment delivers a combination of short-acting bronchodilators via nebulizer. This combo includes salbutamol sulfate and ipratropium bromide, which work quickly to open up the airways and make breathing easier. Researchers are excited because this delivery method could offer faster relief during acute COPD symptoms, potentially improving patient comfort and reducing the need for hospitalization.

What is the effectiveness track record for bronchodilators in treating COPD?

In this trial, participants will receive a combination of salbutamol (also known as albuterol) and ipratropium bromide. Studies have shown that this combination helps people with COPD breathe more easily. It not only opens the airways but also reduces breathlessness and facilitates exercise. Research indicates that this combination is more effective than using either drug alone. One study demonstrated improved lung function and reduced shortness of breath during physical activity. It also decreases the frequency of COPD flare-ups. Overall, this treatment provides significant relief for people with COPD. ^{1 2 3 4 5}

Who Is on the Research Team?

J Alberto Neder, MD, PhD

Principal Investigator

Queen's University

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bronchodilators

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Long-term therapy with ipratropium significantly improved baseline lung function (FEV1 and FVC) in COPD patients, particularly in ex-smokers, while beta-agonists showed no significant changes in lung function.

Extended use of ipratropium not only enhanced baseline lung function but also improved the response to short-term bronchodilation, whereas extended beta-agonist therapy led to a decreased response to acute bronchodilation.

NCBI (Pubmed)

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. Rennard, SI., Serby, CW., Ghafouri, M., et al.[2019]

In a study of 246 COPD patients, those treated with nebulized long-acting β2-agonists (neb-LABAs) had a 47% lower risk of hospital readmission within 6 months after discharge compared to those treated with nebulized short-acting β2-agonists (neb-SABAs).

The study highlights the potential benefits of using neb-LABAs for managing COPD symptoms post-hospitalization, suggesting they may improve patient outcomes and reduce the likelihood of future hospital visits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Readmission Risk in Chronic Obstructive Pulmonary Disease Patients: Comparative Study of Nebulized &#946;2-Agonists. Bollu, V., Guérin, A., Gauthier, G., et al.[2020]

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]

In a study of 109 patients with moderate COPD, formoterol 9 μg demonstrated a significantly faster onset of bronchodilation compared to salmeterol 50 μg, with a 7.2% increase in FEV₁ at 5 minutes post-dose versus 4.1% for salmeterol.

Formoterol also resulted in a higher proportion of patients (23.1%) achieving a ≥12% increase in FEV₁ at 5 minutes compared to salmeterol (9.2%) and placebo (6.4%), indicating its superior efficacy in improving lung function shortly after administration.

NCBI (Pubmed)

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. Cazzola, M., Paggiaro, P., Palange, P., et al.[2021]

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]

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 systematic review of five trials involving 5,920 participants, indacaterol demonstrated significant improvements in reducing the need for rescue medication and alleviating dyspnea compared to tiotropium, with a 43% greater likelihood of achieving clinically meaningful improvements.

Indacaterol also outperformed other long-acting β2-agonists (TD-LABAs) in enhancing lung function (FEV1) and health status, while maintaining similar safety and tolerability profiles to both tiotropium and TD-LABAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

A review of five large trials involving over 1000 COPD patients each found that long-acting bronchodilators had only small effects on patient outcomes, with only half of the primary outcomes being statistically significant.

The studies often focused on statistically significant results rather than clinically meaningful outcomes, which may limit the applicability of these findings to everyday COPD patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Megatrials for bronchodilators in chronic obstructive pulmonary disease (COPD) treatment: time to reflect. van Dijk, WD., van den Bemt, L., van Weel, C.[2013]

Bronchodilators are essential for managing chronic obstructive pulmonary disease (COPD) and asthma, working by relaxing airway smooth muscle cells, with three main classes available: β(2)-adrenoceptor agonists, muscarinic receptor antagonists, and xanthines.

New strategies focus on improving adherence to treatment by developing once-daily dosing options for long-acting bronchodilators, such as indacaterol and glycopyrronium bromide, which aim to simplify management of these airways disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacology and therapeutics of bronchodilators. Cazzola, M., Page, CP., Calzetta, L., et al.[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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4934560/

Efficacy and safety of ipratropium bromide/salbutamol ... In addition to bronchodilation, they improve dyspnea scores, exercise tolerance, promote sleep quality, decrease COPD exacerbations, and improve ...

2. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/414245

For COPD a Combination of Ipratropium Bromide and ... Our study results confirm that a fixed-dose combination of ipratropium bromide and albuterol sulfate is more effective than albuterol base alone in patients ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0012369216387219

In Chronic Obstructive Pulmonary Disease, a Combination ... We conclude that the combination of ipratropium and albuterol, when given by metered-dose inhaler to patients with COPD, is more effective than either of the ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02182856?term=ALBUTEROL%20AND%20IPRATROPIUM&viewType=Table&rank=1

Ipratropium or Salbutamol Sulphate Alone or Combination ... Study to compare the effects of nebulised salbutamol or ipratropium alone in patients with COPD with those of combined salbutamol and ipratropium nebuliser ...

5. atsjournals.org atsjournals.org/doi/full/10.1513/pats.200505-047SR

Combination Therapy for Chronic Obstructive Pulmonary ... In a recent 29-day study of 357 patients with COPD, ipratropium and albuterol was superior to albuterol alone with respect to peak FEV1 and mean ...