ICS/LABA Therapy for Asthma Non-adherence

Recruiting at 1 trial location

Overseen By Tammy Quinones

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Washington University School of Medicine

Must be taking: ICS, SABA

Must not be taking: Biologics, Investigational treatments

Disqualifiers: COPD, Cystic fibrosis, ICU admission, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new inhaler approach for people with asthma who often forget or struggle to use their inhalers regularly. It focuses on individuals diagnosed with mild or moderate persistent asthma who have not adhered to their prescribed inhaler routine, resulting in partly controlled or moderately uncontrolled symptoms. Participants will either use an as-needed inhaled treatment (Budesonide/Formoterol, an ICS/LABA therapy) or continue their usual inhaler routine. Those with asthma for at least six months, a history of not refilling inhalers as expected, and partly controlled symptoms might be suitable candidates. Participants need a smartphone and must be willing to use a device that tracks inhaler use. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications. However, you must be on maintenance ICS treatment and as-needed SABA for at least 6 months before joining. You cannot be using a biologic medication or investigational treatment for asthma.

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

Research shows that combining budesonide and formoterol is generally safe for people with mild asthma. Studies have not identified any new safety issues when these medications are used together. In fact, using budesonide-formoterol as needed reduces the risk of asthma attacks compared to budesonide alone. Patients experienced fewer severe asthma episodes with this inhaler method. While all medications can have side effects, evidence suggests that budesonide-formoterol is a safe choice for managing asthma symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the new approach of using budesonide/formoterol for asthma because, unlike the standard routine of daily maintenance inhalers, this treatment offers a symptom-driven strategy. Most treatments involve regular dosing of inhaled corticosteroids (ICS) combined with as-needed short-acting beta-agonists (SABA). In contrast, budesonide/formoterol allows for on-demand use, combining an inhaled corticosteroid with a long-acting beta-agonist (LABA). This could improve adherence and provide more immediate relief, potentially making asthma management more flexible and effective for patients.

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

Research shows that Budesonide/Formoterol, which participants in this trial may receive as part of the symptom-driven ICS/LABA treatment strategy, effectively manages asthma. Studies have found that this treatment reduces asthma attacks and improves lung function. For example, one study found that patients using Budesonide/Formoterol had fewer asthma attacks compared to those using albuterol. Another study showed that this treatment reduced severe asthma attacks when used as both a regular and emergency inhaler. Overall, the evidence supports its effectiveness in controlling asthma symptoms and reducing hospital visits. ^{5 6 7 8 9}

Who Is on the Research Team?

James Krings, MD MSc

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for people aged 12-75 with mild or moderate persistent asthma who have been prescribed maintenance inhalers and as-needed SABA but are not using their inhalers regularly. They must own a smartphone, have missed at least two ICS refills in the past six months, and have partially controlled to moderately uncontrolled asthma.

Inclusion Criteria

You are between 12 and 75 years old when you join the study.

You have been diagnosed with mild or moderate persistent asthma and have been using certain medications for at least 6 months.

Able to understand and provide informed consent.

Exclusion Criteria

You have certain lung diseases like chronic obstructive pulmonary disease (COPD), cystic fibrosis, or alpha 1 anti-trypsin deficiency.

Unwillingness to use or pay for an inhaler that is compatible with the Adherium sensor (fluticasone propionate or budesonide/formoterol). Of note, fluticasone and budesonide/formoterol are formulary tier 1-2 for Missouri Medicaid and most commercial insurances and are believed to be equally or less expensive as alternative inhalers for most patients.

Patients who do not complete at least 70% of the twice-daily texts during the two weeks after screening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive symptom-driven ICS/LABA treatment or continue standard therapy for 24 weeks

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide/Formoterol

Trial Overview The study compares adherence to budesonide/formoterol taken only when symptoms occur versus regular use of maintenance ICS plus symptom-driven SABA. It aims to address the issue of patients not sticking to daily inhaler routines by testing a new method that matches medication intake with symptom occurrence.

How Is the Trial Designed?

Group I: As needed inhaled corticosteroid and long-acting beta-agonist Active Control 1 Intervention

Symptom-driven ICS/LABA treatment strategy

Group II: Standard therapy: maintenance inhaled corticosteroid and as needed short-acting beta-agonist Active Control 1 Intervention

Continue maintenance ICS and SABA therapy

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Center for Advancing Translational Sciences (NCATS)

Collaborator

Trials

394

Recruited

404,000+

Published Research Related to This Trial

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 study of 2,213 asthmatic patients, those using dry powder inhalers (DPIs) showed lower medication compliance compared to those using pressurized metered-dose inhalers (pMDIs), indicating that the type of inhaler can significantly affect adherence to asthma treatment.

Factors such as age, severity of asthma, and comorbidities influenced compliance, with younger patients and those experiencing more exacerbations being more likely to adhere to their medication regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Identification of factors involved in medication compliance: incorrect inhaler technique of asthma treatment leads to poor compliance. Darbà, J., Ramírez, G., Sicras, A., et al.[2020]

In a study of 232 children with asthma, those prescribed once-daily inhaled corticosteroids (ICS) showed significantly better adherence (66.8% of prescribed days covered) compared to those on a twice-daily regimen (57.9%).

Children on once-daily ICS had a 7.2% higher mean adherence and were more likely to achieve at least 75% adherence, suggesting that simplifying the dosing schedule may improve medication compliance in pediatric asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to inhaled corticosteroids prescribed once vs twice daily in children with asthma. Drouin, O., Smyrnova, A., Bétinjané, N., et al.[2022]

Patients with asthma using the once-daily inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) fluticasone furoate/vilanterol (FF/VI) showed significantly better medication adherence compared to those using the twice-daily options budesonide/formoterol (B/F) and fluticasone propionate/salmeterol (FP/SAL), with mean adherence rates of 0.453 versus 0.345 and 0.446 versus 0.341, respectively.

The study also found that patients on FF/VI had a higher likelihood of maintaining their treatment over time, indicating that once-daily dosing may enhance both adherence and persistence in asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs. Averell, CM., Stanford, RH., Laliberté, F., et al.[2021]

An electronic decision aid was developed to help patients with mild asthma understand the benefits and drawbacks of using as-needed budesonide-formoterol versus daily inhaled corticosteroids, based on user preferences and clinical outcomes.

The decision aid was refined through feedback from 21 asthma patients and 5 physicians over 5 cycles, resulting in a more user-friendly tool that includes simplified information and infographics, which can enhance patient-provider discussions at the point of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A patient decision aid for mild asthma: Navigating a new asthma treatment paradigm. Gagné, M., Lam Shin Cheung, J., Kouri, A., et al.[2022]

In a 24-week study involving 111 asthma patients, the use of a combination inhaler containing both an inhaled corticosteroid (ICS) and a long-acting beta-agonist (LABA) did not significantly improve adherence to medication compared to using separate inhalers.

Adherence rates were similar across both groups, with mean adherence at 82.4% for the combination inhaler, indicating that combining medications into one inhaler may not be as effective in improving adherence as previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled trial of adherence with single or combination inhaled corticosteroid/long-acting beta-agonist inhaler therapy in asthma. Perrin, K., Williams, M., Wijesinghe, M., et al.[2010]

Combination therapy using inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is effective for adults with moderate to severe asthma, simplifying treatment and improving control.

Budesonide/formoterol and salmeterol/fluticasone are both effective and well-tolerated, with budesonide/formoterol offering rapid relief and the flexibility of once-daily dosing for maintenance and as needed for symptom relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination inhalers containing inhaled corticosteroids and long-acting beta2-agonists: improved clinical efficacy and dosing options in patients with asthma. Ankerst, J.[2017]

Budesonide/formoterol (BUD/FORM) in a fixed dose is significantly more effective than budesonide (ICS alone) in reducing treatment failure rates in adults with moderate to severe asthma, with a 50% increased risk of treatment failure associated with budesonide.

Adjustable maintenance dosing of BUD/FORM shows advantages over fixed dosing, including a 28% reduced risk of hospitalizations and a 19% reduced risk of needing oral steroids, highlighting its potential for better management of asthma exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of budesonide/formoterol in a single inhaler. Edwards, SJ., Gruffydd-Jones, K., Ryan, DP.[2018]

Budesonide/formoterol maintenance and reliever therapy significantly reduces the rate of severe asthma exacerbations compared to fixed combination therapies, making it an effective treatment option for moderate-to-severe asthma.

This therapy is also more cost-effective, costing 496 euros per patient over 6 months, which is 78-101 euros less than traditional combination treatments, and has a high probability (> 93%) of being cost-effective in Finland.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of budesonide/formoterol maintenance and reliever therapy versus fixed combination treatments for asthma in Finland*. Tamminen, K., Laine, J., Soini, E., et al.[2019]

In a study of 2598 asthma patients using the MASK-air app, adherence to inhaled corticosteroids plus long-acting β2-agonists (ICS+LABA) was found to be lower for ICS+formoterol (59.3%) compared to ICS with other LABAs (75.1%).

Despite lower adherence, ICS+formoterol users experienced less reliance on short-acting beta-agonists (SABA), indicating that even with lower adherence, they maintained similar asthma control compared to those using other LABAs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to inhaled corticosteroids and long-acting β2-agonists in asthma: A MASK-air study. Sousa-Pinto, B., Louis, R., Anto, JM., et al.[2023]

In a pooled analysis of two 52-week studies involving adolescents with mild asthma, as-needed budesonide-formoterol (BUD-FORM) was found to significantly reduce severe exacerbations compared to as-needed terbutaline, while showing similar efficacy to maintenance budesonide.

As-needed BUD-FORM also demonstrated a greater increase in height among younger adolescents compared to maintenance budesonide, indicating a potential benefit in growth, and no new safety concerns were identified, making it a viable alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of As-Needed Budesonide-Formoterol in Adolescents with Mild Asthma. Reddel, HK., O'Byrne, PM., FitzGerald, JM., et al.[2021]

Combination inhaled corticosteroid and long-acting β(2)-agonist (ICS/LABA) medications, like fluticasone/salmeterol and budesonide/formoterol, show similar efficacy and tolerability, and improve adherence compared to taking the medications separately.

Patients prefer asthma medications that provide a rapid onset of relief and long-lasting effects, which can enhance satisfaction and adherence to treatment, highlighting the need for future therapies that combine effective anti-inflammatory and bronchodilator properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of moderate to severe asthma: patient perspectives on combination inhaler therapy and implications for adherence. Murphy, KR., Bender, BG.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12024486/

Real-Life Effectiveness of Budesonide/Formoterol as ... The evidence from the real-life NOTOS study showed significant and clinically meaningful improvement in asthma control, lung function, and ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1901963

Controlled Trial of Budesonide–Formoterol as Needed for ... Primary Outcome​​ The asthma exacerbation rate in the budesonide–formoterol group was lower than that in the albuterol group (absolute rate per ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25439363/

Comparative effectiveness of budesonide-formoterol ... Asthma exacerbation was lower for BFC versus FSC initiators due to lower rates of oral corticosteroid use and asthma-related emergency department visits.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2789512

Evaluation of Budesonide-Formoterol for Maintenance and ... This systematic review and meta-analysis evaluates whether, for patients with poorly controlled asthma, switching to single inhaler ...

5. thelancet.com thelancet.com/journals/lanres/article/PIIS2213-2600(13)70007-9/abstract

a randomised controlled trial The Single combination budesonide–formoterol inhaler Maintenance And Reliever Therapy (SMART) regimen reduces severe asthma exacerbations in patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7994217/

Safety of As-Needed Budesonide-Formoterol in Mild Asthma Budesonide-formoterol anti-inflammatory reliever therapy is generally well-tolerated in patients with mild asthma. No new safety concerns were ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa1715274

Inhaled Combined Budesonide–Formoterol as Needed in ... With respect to the mean percentage of weeks with well-controlled asthma per patient, budesonide–formoterol was superior to terbutaline (34.4% ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2213219823003987

Safety and Effectiveness of As-Needed Formoterol in ... As-needed formoterol significantly reduced exacerbation risk compared with as-needed salbutamol when added to maintenance ICS-formoterol, but not to ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27579635/

Serious Asthma Events with Budesonide plus Formoterol ... The risk of an asthma exacerbation was 16.5% lower with budesonide-formoterol than with budesonide (hazard ratio, 0.84; 95% CI, 0.74 to 0.94; P= ...