Inhaled Steroids/Long-Acting Bronchodilators for Asthma

Overseen By Arthur F Gelb, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Gelb, Arthur F., M.D.

Must be taking: Inhaled corticosteroids, Long acting beta2agonists

Disqualifiers: Pregnancy

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the site and mechanisms responsible for expiratory airflow limitation in chronic, treated, non-smoking, stable asthmatics with moderate to severe persistent expiratory airflow obstruction. Treatment will include inhaled corticosteroids and long acting beta2agonists. The investigators are interested in determining whether the large and/or small airways are the predominant site of airflow limitation. The investigators are also interested in determining whether intrinsic small airways obstruction and/or loss of lung elastic recoil is responsible for expiratory airflow limitation. The investigators are also interested to evaluate the role of varying doses of inhaled corticosteroids to suppress large and small airway inflammation using exhaled nitric oxide as surrogate markers of inflammation. For comparison purposes, spirometry and measurements of exhaled nitric oxide will also be obtained if possible during a naturally occurring exacerbation of asthma.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications. However, since it involves treatment with inhaled corticosteroids and long-acting bronchodilators, you may need to adjust your current asthma medications. Please consult with the trial coordinators for specific guidance.

What data supports the effectiveness of the drug Budesonide/Formoterol, Fluticasone/Salmeterol, Advair, Seretide, AirDuo Respiclick, Fluticasone Propionate/Salmeterol Xinafoate for asthma?

Research shows that the combination of fluticasone propionate and salmeterol (found in drugs like Advair and Seretide) is effective in improving lung function and asthma symptoms more than using inhaled corticosteroids alone. It is also well tolerated and cost-effective for maintaining asthma control. ^{1 2 3 4 5}

Is the combination of inhaled steroids and long-acting bronchodilators safe for asthma patients?

Studies show that using inhaled steroids with long-acting bronchodilators, like budesonide/formoterol, is generally safe for asthma patients. Common side effects include oral thrush (a mouth infection), tremors, and throat pain, but serious issues are rare. Long-term use has not shown significant safety concerns, and it may even reduce asthma flare-ups. ^{6 7 8 9 10}

How does the drug Budesonide/Formoterol differ from other asthma treatments?

Budesonide/Formoterol is a combination of an inhaled steroid and a long-acting bronchodilator, which helps to control asthma symptoms by reducing inflammation and relaxing the muscles around the airways. It is similar to Fluticasone/Salmeterol, but studies suggest that Fluticasone/Salmeterol may provide better asthma control and lung function improvement in some patients. ^{1 3 4 11 12}

Research Team

Arthur F Gelb, MD

Principal Investigator

Arthur F Gelb Medical Corporation

Eligibility Criteria

This trial is for stable, treated asthmatics aged 10-80 who are current non-smokers with a minimal smoking history. Participants should have specific levels of lung function reduction after using albuterol. Pregnant individuals cannot participate.

Inclusion Criteria

I am between 10 and 80 years old.

My lung function tests show severe asthma or COPD.

My asthma is under control with treatment.

Exclusion Criteria

Pregnancy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive inhaled corticosteroids and long-acting beta2 agonists to evaluate airflow limitation mechanisms

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including spirometry and exhaled nitric oxide measurements

4 weeks

Long-term Observation

Long-term observation to evaluate mechanisms of expiratory airflow limitation and presence of emphysema

1-5 years

Treatment Details

Interventions

• Budesonide/Formoterol
• Fluticasone/Salmeterol

Trial Overview The study tests the effects of two inhaled treatments: budesonide/formoterol and fluticasone/salmeterol on airflow limitation in asthma patients. It aims to identify which airways are affected and how inflammation can be reduced using different doses.

Participant Groups

Group I: Asthma observational study arm Experimental Treatment 2 Interventions

Asthmatics in this arm may be on varying dose of inhaled fluticasone 100-500mcg/salmeterol 50mcg bid via Advair MDI or equivalent dose via Diskus bid or Symbicort (budesonide 80-160mcg/formoterol 4.5mcg bid)or Dulera 100-200mcg mometasone/5 mcg formoterol bid, tiotropium 18mcg capsule daily. This is an observational study and additional pharmacologic intervention may include antibiotic and tapering doses of corticosteroids.

Who Is Running the Clinical Trial?

Gelb, Arthur F., M.D.

Lead Sponsor

Trials

7

Recruited

350+

Findings from Research

Salmeterol/fluticasone propionate, administered via inhalers, is at least as effective as separate treatments for improving lung function and asthma symptoms, making it a reliable maintenance therapy for asthma patients.

In a well-designed 1-year study, this combination therapy was shown to be more effective than adjusted-dose budesonide/formoterol and is considered a cost-effective option compared to other asthma treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled salmeterol/fluticasone propionate: a review of its use in asthma. Reynolds, NA., Lyseng-Williamson, KA., Wiseman, LR.[2021]

Fluticasone propionate/formoterol fumarate (FP/FORM) combination therapy improved lung function in children with asthma, showing similar efficacy to fluticasone propionate/salmeterol (FP/SAL) over a 12-week period, with no significant differences in safety or tolerability between the two treatments.

The study involved 211 children aged 4-12 years, and both therapies were well-tolerated, with FP/FORM showing no adverse effects on plasma cortisol levels, indicating it is a safe long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 12-week open-label, randomized, controlled trial and 24-week extension to assess the efficacy and safety of fluticasone propionate/formoterol in children with asthma. Emeryk, A., Klink, R., McIver, T., et al.[2018]

Fluticasone propionate/salmeterol (Advair) is an effective treatment for chronic obstructive pulmonary disease (COPD), improving lung function, reducing symptoms, and enhancing quality of life for some patients.

This combination inhaler not only acts as a potent bronchodilator but also helps decrease the frequency of exacerbations in patients with more severe COPD, although careful patient selection is important for optimal outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone propionate/salmeterol for the treatment of chronic-obstructive pulmonary disease. Dransfield, MT., Bailey, WC.[2019]

Salmeterol/fluticasone propionate significantly improves lung function and asthma symptoms compared to inhaled corticosteroids alone, with benefits sustained over a year in a well-designed trial involving symptomatic asthma patients.

This combination therapy is generally well tolerated across different age groups and offers a corticosteroid-sparing effect, making it a cost-effective option for asthma maintenance treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salmeterol/fluticasone propionate: a review of its use in asthma. McKeage, K., Keam, SJ.[2021]

Fluticasone propionate/formoterol (flutiform) significantly improved lung function in asthma patients compared to both Skyepharma fluticasone and GSK fluticasone, with a mean difference in FEV1 of 0.161 L and 0.185 L respectively, indicating its superior efficacy.

The safety profile of fluticasone/formoterol was comparable to that of fluticasone alone, with fewer treatment-emergent adverse events (32.9%) compared to the other formulations (39.7% for SKP FP and 40.4% for GSK FP).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority of fluticasone propionate/formoterol fumarate versus fluticasone propionate alone in patients with moderate-to-severe asthma: a randomised controlled trial. Pertseva, T., Dissanayake, S., Kaiser, K.[2015]

Budesonide/formoterol is associated with a significantly lower incidence of pneumonia adverse events compared to salmeterol/fluticasone, with an odds ratio of 0.47, based on a systematic review of 12 trials involving both treatments.

The analysis also found that serious pneumonia adverse events were significantly lower with budesonide/formoterol (odds ratio of 0.41), suggesting it may be a safer option for patients with chronic obstructive pulmonary disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Budesonide/formoterol vs. salmeterol/fluticasone in COPD: a systematic review and adjusted indirect comparison of pneumonia in randomised controlled trials. Halpin, DM., Gray, J., Edwards, SJ., et al.[2022]

In a study involving 40 adult asthmatics, the pressurized metered-dose inhaler (pMDI) with extra-fine particles (FORM/BDP) showed a greater improvement in lung function compared to the pMDI with non-extra-fine particles (FORM/BUD), although overall treatment outcomes were similar between the two.

Patient preferences indicated that while FORM/BDP was perceived to have a higher flume velocity and was more effective in reaching the trachea and bronchus, it also caused more irritation than FORM/BUD, highlighting the importance of patient experience in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Two pMDIs in Adult Asthmatics: A Randomized Double-Blind Double-Dummy Clinical Trial. Nam, TH., Kang, SY., Lee, SM., et al.[2022]

In a study involving 11,693 patients with persistent asthma, the combination of budesonide and formoterol was found to have a similar risk of serious asthma-related events compared to budesonide alone, demonstrating its safety in this context.

Patients treated with budesonide-formoterol experienced a 16.5% lower risk of asthma exacerbations compared to those on budesonide, indicating that this combination therapy is more effective in managing asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. Peters, SP., Bleecker, ER., Canonica, GW., et al.[2017]

In a 52-week study involving 708 patients with moderate to severe asthma, the combination of budesonide/formoterol showed a significantly lower rate of asthma exacerbations compared to budesonide alone, indicating improved efficacy in asthma management.

The safety profile of budesonide/formoterol was acceptable, with no significant differences in adverse events or clinical abnormalities compared to budesonide, suggesting that adding a long-acting beta(2)-adrenergic agonist (LABA) to inhaled corticosteroids (ICSs) is safe for long-term use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients. Peters, SP., Prenner, BM., Mezzanotte, WS., et al.[2022]

In a study involving 512 children aged 5-12 with persistent asthma, fluticasone propionate/formoterol was found to be superior to fluticasone alone in improving lung function, as measured by FEV1, over 12 weeks.

Fluticasone/formoterol was non-inferior to fluticasone/salmeterol, indicating it is as effective as this combination treatment, while all treatments were well tolerated with few severe exacerbations reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial. Płoszczuk, A., Bosheva, M., Spooner, K., et al.[2019]

In a review of five studies involving 5537 participants, fluticasone/salmeterol showed a lower odds ratio for exacerbations requiring oral steroids compared to budesonide/formoterol, although this difference was not statistically significant, indicating a potential but uncertain benefit.

Both treatments demonstrated similar efficacy in lung function and overall asthma management, suggesting that neither therapy is clearly superior, and further research is needed to clarify their relative safety and effectiveness, especially in children under 12.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children. Lasserson, TJ., Ferrara, G., Casali, L.[2020]

In a study involving adults with asthma, fluticasone/formoterol demonstrated a faster onset of bronchodilation compared to fluticasone/salmeterol, with nearly four times the odds of achieving bronchodilation within 5 minutes after dosing on day 0.

Over 12 weeks, fluticasone/formoterol consistently provided greater improvements in lung function (FEV1) compared to fluticasone/salmeterol, suggesting it may enhance treatment adherence for asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Onset of bronchodilation with fluticasone/formoterol combination versus fluticasone/salmeterol in an open-label, randomized study. Aalbers, R., Brusselle, G., McIver, T., et al.[2017]

References

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

Inhaled salmeterol/fluticasone propionate: a review of its use in asthma. [2021]

2. England pubmed.ncbi.nlm.nih.gov

A 12-week open-label, randomized, controlled trial and 24-week extension to assess the efficacy and safety of fluticasone propionate/formoterol in children with asthma. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Fluticasone propionate/salmeterol for the treatment of chronic-obstructive pulmonary disease. [2019]

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

Salmeterol/fluticasone propionate: a review of its use in asthma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Superiority of fluticasone propionate/formoterol fumarate versus fluticasone propionate alone in patients with moderate-to-severe asthma: a randomised controlled trial. [2015]

6. India pubmed.ncbi.nlm.nih.gov

Budesonide/formoterol vs. salmeterol/fluticasone in COPD: a systematic review and adjusted indirect comparison of pneumonia in randomised controlled trials. [2022]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Comparison of Two pMDIs in Adult Asthmatics: A Randomized Double-Blind Double-Dummy Clinical Trial. [2022]

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

Serious Asthma Events with Budesonide plus Formoterol vs. Budesonide Alone. [2017]

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

Long-term safety and asthma control with budesonide/formoterol versus budesonide pressurized metered-dose inhaler in asthma patients. [2022]

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

Efficacy and safety of fluticasone propionate/formoterol fumarate in pediatric asthma patients: a randomized controlled trial. [2019]

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

Combination fluticasone and salmeterol versus fixed dose combination budesonide and formoterol for chronic asthma in adults and children. [2020]

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

Onset of bronchodilation with fluticasone/formoterol combination versus fluticasone/salmeterol in an open-label, randomized study. [2017]