ICS for COPD

Overseen By Jennifer Biondo

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether adding inhaled corticosteroids (ICS) to regular treatment can improve lung function in people with stable chronic obstructive pulmonary disease (COPD). The study tests different medication combinations to determine which best increases lung blood flow when using an inhaler. Participants must have a COPD diagnosis, a history of smoking, and regular use of certain COPD medications. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in COPD treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the treatments in this trial, Bretzri and Bevespi, have been tested for safety in people with COPD, a lung condition that makes breathing difficult.

Bretzri combines three medications: budesonide, glycopyrronium, and formoterol. Studies have found it to be generally well tolerated, with most side effects being mild or moderate. The most common side effects included pneumonia, low potassium levels, and upper respiratory infections, though these were infrequent.

Bevespi contains two medications: glycopyrrolate and formoterol. It also has a good safety record. The most common side effects were cough and urinary tract infections, occurring in less than 5% of patients.

Both treatments have been used in other studies, and their safety is well understood. Participants in this trial can feel confident that these treatments have been researched for safety in people with similar conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial because they explore the use of inhaled corticosteroids (ICS) in combination with two specific inhalers, Bretzri and Bevespi, for COPD management. Unlike standard treatments like long-acting bronchodilators or standalone ICS, these combinations might offer improved lung function and symptom control by sequentially targeting inflammation and airway constriction. The novel approach of alternating these inhalers over a set period could potentially optimize the therapeutic benefits, offering a tailored strategy for COPD patients.

What evidence suggests that this trial's treatments could be effective for COPD?

This trial will compare two treatment sequences for COPD. Research has shown that inhaled corticosteroids (ICS), such as those in Bretzri, can greatly reduce flare-ups in people with COPD. One study found that a treatment combining three medications, including ICS, led to a 13% reduction in moderate to severe COPD flare-ups. This treatment was effective without causing serious heart or lung problems.

Participants in one arm of this trial will receive Bretzri followed by Bevespi. Bevespi, another treatment studied, has also shown positive results. It significantly improves lung function in COPD patients compared to its individual components alone. Participants in the other arm will receive Bevespi followed by Bretzri. Both treatments have been well-tolerated, indicating they are good options for managing COPD symptoms. ^{2 4 6 7 8}

Who Is on the Research Team?

Adam Wanner, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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.

You had high blood pressure in the right side of your heart during a previous heart ultrasound.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled Corticosteroids (ICS)

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.

How Is the Trial Designed?

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+

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

Published Research Related to This Trial

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) 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]

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]

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]

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 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]

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]

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]

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]

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) 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]

Citations

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New developments in optimizing bronchodilator treatment of ... Now that several LAMA/LABA FDCs have been approved for use in COPD, we review the impact of dual-bronchodilator treatment on COPD therapy and discuss recent ...

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Bevespi Aerosphere demonstrates statistically significant ... Bevespi Aerosphere demonstrates statistically significant improvement in lung function in patients with COPD · Phase III, PINNACLE 4 trial ...

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COPD: Positive Lung Function Results for Bevespi Aerosphere COPD therapy Bevespi Aerosphere demonstrated a statistically significant improvement in lung function compared to its monotherapy components and placebo, ...

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Safety and efficacy of budesonide/glycopyrrolate/formoterol ... The current study demonstrated that BGF significantly improved lung function compared with GFF in individuals with moderate to severe COPD at ...

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Safety & Side Effects Find side effects, safety, and risk information related to BEVESPI AEROSPHERE. Ask your health care provider if you have any questions.

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COPD Patient Profile - BEVESPI Aerosphere The most common adverse reactions with BEVESPI (≥2% and more common than placebo) were cough, 4.0% (2.7%) and urinary tract infection, 2.6% (2.3%). DRUG ...

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208294Orig1s000 - accessdata.fda.gov Safety findings are discussed in Section 8. Table 1. Relevant clinical studies with glycopyrrolate and formoterol fumarate combination drug.