ICS/LABA Therapy for Asthma Non-adherence

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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

Inhaler nonadherence is a common problem that has been estimated to account for approximately 60% of all asthma-related hospitalizations. Unfortunately, prior interventions to improve inhaler nonadherence have shown a lack of long-term success. This study proposes to assess the problem of non-adherence using a D\&I research lens while testing a new inhaler approach to potentially ameliorate the detrimental consequences of maintenance inhaler nonadherence.

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.

What data supports the idea that ICS/LABA Therapy for Asthma Non-adherence (also known as: Budesonide/Formoterol) is an effective treatment?

The available research shows that Budesonide/Formoterol, a combination inhaler therapy, is effective in managing asthma. It has similar effectiveness and tolerability compared to other combination treatments like Fluticasone/Salmeterol. Studies indicate that adherence to Budesonide/Formoterol is higher than when the components are taken separately, which is important because better adherence leads to better asthma control. Additionally, in adolescents with mild asthma, using Budesonide/Formoterol as needed reduces severe asthma attacks more effectively than using short-acting medications alone. ^{1 2 3 4 5}

What safety data is available for Budesonide/Formoterol in asthma treatment?

Safety data for Budesonide/Formoterol indicates that it is effective in reducing severe exacerbations in both mild and moderate/severe asthma. A postmarketing safety study evaluated by the FDA found no increased risk of serious asthma-related events when formoterol was added to budesonide maintenance therapy. However, there are concerns about the safety of adding long-acting β2-agonists to inhaled glucocorticoids, which are addressed in ongoing studies. ^{1 6 7 8 9}

Is the drug Budesonide/Formoterol a promising treatment for asthma non-adherence?

Yes, Budesonide/Formoterol is a promising treatment for asthma non-adherence because it combines two medications in one inhaler, making it easier for patients to stick to their treatment. This combination has been shown to improve adherence and control asthma symptoms effectively. ^{3 6 10 11 12}

Research Team

James Krings, MD MSc

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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.

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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]

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 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]

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 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]

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]

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]

References

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

Efficacy and Safety of As-Needed Budesonide-Formoterol in Adolescents with Mild Asthma. [2021]

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

Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs. [2021]

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

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

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

Identification of factors involved in medication compliance: incorrect inhaler technique of asthma treatment leads to poor compliance. [2020]

5. Spain pubmed.ncbi.nlm.nih.gov

Adherence to inhaled corticosteroids and long-acting β2-agonists in asthma: A MASK-air study. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Systematic review and meta-analysis of budesonide/formoterol in a single inhaler. [2018]

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

A patient decision aid for mild asthma: Navigating a new asthma treatment paradigm. [2022]

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

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

9. England pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of budesonide/formoterol maintenance and reliever therapy versus fixed combination treatments for asthma in Finland*. [2019]

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

Randomized controlled trial of adherence with single or combination inhaled corticosteroid/long-acting beta-agonist inhaler therapy in asthma. [2010]

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

Adherence to inhaled corticosteroids prescribed once vs twice daily in children with asthma. [2022]

12. England 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. [2017]