ICS for COPD

Overseen by Adam Wanner, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Miami

Must be taking: LAMA/LABA

Must not be taking: ICS, Beta-blockers, Glucocorticosteroids

Disqualifiers: Pregnancy, Recent COVID, Smoking, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

The study objective is to determine whether an ICS added for 4 weeks to a baseline treatment with a Long-Acting Beta-adrenergic Agonist (LABA) and Long-Acting Muscarinic Antagonist (LAMA) combination improves pulmonary vascular endothelial function as assessed by the vasodilator response to inhaled albuterol (endothelium-dependent vasodilation) in stable COPD patients treated with a LABA/LAMA without an ICS for at least one month.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop using inhaled corticosteroids (ICS) at least 4 weeks before joining. You also cannot use beta-blockers, systemic glucocorticosteroids within 6 weeks prior, or regular pulmonary vasodilators. If you're on these medications, you may need to stop them to participate.

What data supports the idea that ICS for COPD is an effective drug?

The available research shows that inhaled corticosteroids (ICS) can reduce the rate and severity of flare-ups in patients with moderate-to-severe COPD and improve their quality of life. Studies indicate that while ICS may not slow down the decline in lung function, they can help manage symptoms and reduce the frequency of exacerbations. Additionally, combining ICS with long-acting beta-2 agonists may offer further benefits compared to using either treatment alone. However, ICS are often overprescribed, and their use should be more selective, focusing on patients who show specific symptoms or have a history of asthma or allergies. ^{1 2 3 4 5}

What safety data exists for inhaled corticosteroids in COPD treatment?

The safety of inhaled corticosteroids (ICS) in COPD treatment is debated. A meta-analysis suggests conflicting evidence on cardiovascular safety, with some studies indicating increased or reduced risk of cardiovascular events. ICS use is associated with an increased risk of pneumonia, with potential differences in risk between fluticasone and budesonide. Overuse of ICS in COPD is common, and guidelines suggest withdrawal in many cases due to risk-benefit imbalances. Overall, the safety profile of ICS in COPD is complex and requires careful consideration. ^{4 6 7 8 9}

Is the drug ICS a promising treatment for COPD?

ICS might help people with moderate-to-severe COPD by reducing flare-ups and improving their quality of life. However, its effectiveness is debated, and it is usually recommended for severe cases. ^{2 10 11 12 13}

Research Team

Adam Wanner, MD

Principal Investigator

University of Miami

Eligibility Criteria

This trial is for former smokers aged 40-80 with a physician's diagnosis of COPD, who have been on a LAMA/LABA regimen for at least one month. They should not be current smokers or have used ICS recently. Participants must not have had certain vaccinations, acute COPD exacerbations, respiratory infections recently, or specific cardiovascular issues.

Inclusion Criteria

I have smoked more than 10 packs of cigarettes a year in the past.

I am between 40 and 80 years old.

My doctor has diagnosed me with COPD.

Exclusion Criteria

I regularly use medication to widen my lung blood vessels.

I haven't taken steroid medications in the last 6 weeks.

Your blood pressure is too high on the test day.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Bretzri for 4 weeks followed by 8 weeks of Bevespi or Bevespi for 8 weeks followed by 4 weeks of Bretzri

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Inhaled Corticosteroids (ICS) (Corticosteroid)

Trial Overview The study tests if adding an inhaled corticosteroid (ICS) to existing treatment with LABA and LAMA improves lung blood vessel function in stable COPD patients. This response is measured after inhaling albuterol over four weeks.

Participant Groups

Group I: Bretzri followed by Bevespi Group Experimental Treatment 2 Interventions

Participants in this group will receive Bretzri for 4-weeks followed by 8-weeks of Bevespi.

Group II: Bevespi followed by Bretzri Group Experimental Treatment 2 Interventions

Participants in this group will receive Bevespi for 8-weeks followed by 4-weeks of Bretzri.

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Sylvia Daunert

University of Miami

Chief Executive Officer since 2011

PhD in Biochemistry and Molecular Biology, University of Kentucky

Bahar Motlagh

University of Miami

Chief Medical Officer since 2021

PhD in Biomedical Engineering, Ecole Polytechnique Montreal

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

Inhaled corticosteroids (ICS) can reduce the number and severity of exacerbations in COPD patients, improving symptoms and quality of life, but they do not prevent the accelerated decline in lung function.

A one-year trial of ICS is recommended for COPD patients with a history of asthma or allergy, focusing on exacerbations and symptoms as primary outcomes, while considering the combined use of ICS with long-acting beta-2 agonists for enhanced efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Inhaled corticosteroids for COPD]. Dekhuijzen, PN.[2006]

Inhaled corticosteroids (ICS) are essential for managing asthma and are underused in elderly patients, highlighting a gap in treatment that could improve their health outcomes.

Recent evidence suggests that ICS can also benefit patients with chronic obstructive pulmonary disease (COPD) by reducing exacerbation rates and improving quality of life, especially in those with moderate-to-severe COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pulmonary diseases in the elderly. Problems of pharmacotherapy]. Ukena, D.[2019]

In a study of 710 COPD patients in France, it was found that the prescription of the fluticasone propionate/salmeterol combination (FSC) did not align well with the approved guidelines, particularly in ICS-naïve patients, where compliance was less than 7%.

The majority of patients had moderate to very severe COPD, indicating a need for better adherence to prescribing practices and regular evaluation of lung function (FEV1) to ensure appropriate treatment management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life use of fluticasone propionate/salmeterol in patients with chronic obstructive pulmonary disease: a French observational study. Roche, N., Pribil, C., Van Ganse, E., et al.[2021]

Inhaled corticosteroids (ICSs) are often overprescribed for COPD patients, with up to 70% receiving them, despite evidence suggesting that many may not benefit from their use.

There is a growing consensus and guidelines recommending the withdrawal of ICSs in many COPD patients, prompting the creation of an educational platform to help physicians adjust their prescribing practices based on recent scientific evidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overuse of inhaled corticosteroids in COPD: five questions for withdrawal in daily practice. Cataldo, D., Derom, E., Liistro, G., et al.[2022]

Inhaled corticosteroids (ICS) do not affect the rate of lung function decline (FEV1) in asymptomatic COPD patients, indicating they should not be routinely prescribed to those with well-preserved lung function.

However, ICS may provide clinical benefits for patients with moderately severe COPD (FEV1 < 50% predicted), including improved lung function, reduced symptoms, and fewer exacerbations, suggesting a more selective use in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled corticosteroids in chronic obstructive pulmonary disease: new trials and old practices. O'Riordan, TG.[2007]

A meta-analysis of 31 randomized trials found that inhaled corticosteroids (ICSs) do not increase the risk of cardiovascular (CV) events in patients with chronic obstructive pulmonary disease (COPD), showing a relative risk of 0.99.

Subgroup analyses indicated that combining ICSs with long-acting β2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs) also did not lead to an increased risk of CV events, reinforcing the safety profile of ICS therapy in COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of Cardiovascular Events Associated with Inhaled Corticosteroid Treatment in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis. Jing, X., Li, Y., Xu, J.[2019]

In a 12-week study involving 744 children aged 6-11 with moderate to severe asthma, ciclesonide demonstrated similar efficacy to fluticasone propionate in improving lung function and asthma control, with significant improvements in FEV1 and morning peak expiratory flow.

Ciclesonide was found to have a better safety profile, as it did not significantly suppress cortisol levels, unlike fluticasone propionate, suggesting it may be a safer option for long-term use in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma. Pedersen, S., Engelstätter, R., Weber, HJ., et al.[2015]

A systematic review of 5 studies involving 57,199 patients found that inhaled fluticasone is associated with a 13.5% increased risk of pneumonia compared to budesonide in COPD patients.

The risk of serious pneumonia is also higher with fluticasone, showing a 14.4% increased risk compared to budesonide, indicating a significant intraclass difference in pneumonia risk between these two inhaled corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraclass Difference in Pneumonia Risk with Fluticasone and Budesonide in COPD: A Systematic Review of Evidence from Direct-Comparison Studies. Lodise, TP., Li, J., Gandhi, HN., et al.[2021]

In a review of 11 randomized controlled trials involving 14,426 participants, inhaled corticosteroid (ICS) therapy did not significantly reduce 1-year all-cause mortality in patients with stable chronic obstructive pulmonary disease (COPD).

However, ICS therapy was linked to a higher incidence of pneumonia, particularly in patients receiving higher doses, those using ICS for shorter durations, and those with lower lung function, indicating a need for careful consideration of risks when prescribing ICS for COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. Drummond, MB., Dasenbrook, EC., Pitz, MW., et al.[2022]

Inhaled corticosteroids (ICS) can reduce the frequency and severity of COPD exacerbations when used with long-acting bronchodilators, but they do not improve overall mortality or significantly affect lung function in COPD patients.

ICS treatment is recommended primarily for patients with grade III or IV COPD, as it can lower severe exacerbations by 39%, but it also increases the risk of pneumonia and has minimal impact on lung function compared to bronchodilators alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Pharmacological Treatment of Chronic Obstructive Pulmonary Disease. Gillissen, A., Haidl, P., Khlhäufl, M., et al.[2023]

A study involving 112 patients over 50 years old showed that after reassessment with spirometry, the diagnosis of asthma increased significantly from 25 to 62 patients, indicating a shift in diagnostic practices among GPs.

Inhaled glucocorticosteroids (ICS) were discontinued in 31 patients, including 20 with mild to moderate COPD and 11 with normal spirometry, highlighting the importance of spirometry in identifying inappropriate ICS use and ensuring better alignment of diagnoses with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changed terms for drug payment influenced GPs' diagnoses and prescribing practice for inhaled corticosteroids. Dalbak, LG., Rognstad, S., Melbye, H., et al.[2021]

In a study of 707 COPD patients, over half (52.4%) with a post-bronchodilator FEV1 of 50% or higher were prescribed inhaled corticosteroids (ICS), despite guidelines recommending ICS only for those with lower FEV1 or frequent exacerbations.

This indicates a significant mismatch between clinical practice and established guidelines, suggesting that many patients may be receiving unnecessary ICS treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inappropriate inhaled corticosteroid prescribing in chronic obstructive pulmonary disease patients. Harrison, A., Borg, B., Thompson, B., et al.[2018]

The use of extrafine BDP/F inhaled corticosteroids significantly improved lung function and reduced hyperinflation in patients with COPD, as shown by various imaging and pulmonary function tests over a 6-month period.

Patients previously on inhaled corticosteroids remained stable on a lower dose of the extrafine formulation, while steroid-naïve patients experienced improvements in hyperinflation, indicating the efficacy of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of extrafine beclometasone/formoterol (BDP/F) on lung function, dyspnea, hyperinflation, and airway geometry in COPD patients: novel insight using functional respiratory imaging. De Backer, J., Vos, W., Vinchurkar, S., et al.[2016]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

[Inhaled corticosteroids for COPD]. [2006]

2. Germany pubmed.ncbi.nlm.nih.gov

[Pulmonary diseases in the elderly. Problems of pharmacotherapy]. [2019]

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

Real-life use of fluticasone propionate/salmeterol in patients with chronic obstructive pulmonary disease: a French observational study. [2021]

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

Overuse of inhaled corticosteroids in COPD: five questions for withdrawal in daily practice. [2022]

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

Inhaled corticosteroids in chronic obstructive pulmonary disease: new trials and old practices. [2007]

6. Egypt pubmed.ncbi.nlm.nih.gov

Risk of Cardiovascular Events Associated with Inhaled Corticosteroid Treatment in Patients with Chronic Obstructive Pulmonary Disease: A Meta-Analysis. [2019]

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

Efficacy and safety of ciclesonide once daily and fluticasone propionate twice daily in children with asthma. [2015]

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

Intraclass Difference in Pneumonia Risk with Fluticasone and Budesonide in COPD: A Systematic Review of Evidence from Direct-Comparison Studies. [2021]

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

Inhaled corticosteroids in patients with stable chronic obstructive pulmonary disease: a systematic review and meta-analysis. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

The Pharmacological Treatment of Chronic Obstructive Pulmonary Disease. [2023]

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

Changed terms for drug payment influenced GPs' diagnoses and prescribing practice for inhaled corticosteroids. [2021]

12. Australia pubmed.ncbi.nlm.nih.gov

Inappropriate inhaled corticosteroid prescribing in chronic obstructive pulmonary disease patients. [2018]

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

The effects of extrafine beclometasone/formoterol (BDP/F) on lung function, dyspnea, hyperinflation, and airway geometry in COPD patients: novel insight using functional respiratory imaging. [2016]