Albuterol + Budesonide for Asthma

(DARWIN Trial)

Recruiting at 15 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: AstraZeneca

Must not be taking: ICS, LAMA, LABA, Corticosteroids

Disqualifiers: Life-threatening asthma, Respiratory disease, Malignancy, Cardiovascular, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of combining two asthma medications, albuterol and budesonide, compared to using albuterol alone. Researchers aim to determine if the combination can better reduce airway inflammation and improve asthma symptoms. The trial targets adults with mild asthma who frequently use their rescue inhaler at least two days a week. Participants will be randomly assigned to use either the combination treatment or albuterol alone for 12 weeks. As a Phase 4 trial, this research seeks to understand how the already FDA-approved treatment benefits more patients, offering an opportunity to contribute to broader asthma care improvements.

Will I have to stop taking my current medications?

The trial requires that you do not use any inhaled corticosteroids (ICS) for maintenance or rescue at enrollment and within 4 weeks of the first visit. Other asthma control therapies like leukotriene receptor antagonists or antihistamines are allowed, but not long-acting muscarinic antagonists (LAMA) or long-acting beta-agonists (LABA).

What is the safety track record for these treatments?

Research has shown that using albuterol with budesonide is safe for people with asthma. Several studies found this combination well tolerated, even with regular use for 12 weeks, and no new safety concerns emerged. Specifically, one study found a 47% lower risk of severe asthma attacks with the combination compared to albuterol alone, indicating fewer serious issues for users. Overall, the safety of this treatment aligns with existing knowledge, making it a reliable option for asthma relief. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about combining albuterol with budesonide for asthma treatment because it offers a potentially more effective rescue therapy. While albuterol is a common fast-acting bronchodilator used to relieve asthma symptoms, adding budesonide, a corticosteroid, can help reduce inflammation in the airways. This combination could provide both immediate relief and longer-lasting control compared to using albuterol alone. By targeting both the symptoms and the underlying inflammation, this treatment has the potential to improve asthma management and reduce flare-ups more effectively than standard albuterol-only options.

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

This trial will compare the effectiveness of albuterol/budesonide with albuterol alone for as-needed rescue therapy in asthma patients. Research has shown that using a mix of albuterol and budesonide when needed can greatly reduce severe asthma flare-ups. One study showed that this combination lowered the risk of severe attacks by 47% compared to using albuterol alone. Another study found a 28% reduction in severe asthma attacks with this mix. These findings suggest that the albuterol-budesonide combination works better than just albuterol for people with mild asthma. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults with mild asthma who need to manage inflammation and symptoms. Participants should be able to commit to a study duration of up to 15 weeks, including clinic visits and video calls.

Inclusion Criteria

I expect to use my rescue inhaler at least 2 days a week.

FeNO level ≥ 25 ppb at Visit 1

I have been diagnosed with asthma by a doctor.

Exclusion Criteria

I am not on any medication or have conditions that affect FeNO levels.

I have a lung condition that is not just allergies.

I have had severe asthma attacks that required breathing support and ICU care.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Lead-In Period

Participants undergo initial assessments and stabilization before treatment

Up to 3 weeks

1 visit (in-person)

Treatment

Participants receive albuterol/budesonide or albuterol for 12 weeks

12 weeks

3 visits (in-person), 2 visits (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Albuterol
• Albuterol/Budesonide

Trial Overview The study is testing the effectiveness of two treatments: albuterol alone versus a combination of albuterol/budesonide. It focuses on how these treatments affect airway inflammation, control asthma symptoms, and reduce the need for rescue therapy over 12 weeks.

How Is the Trial Designed?

Group I: Group 1 - Participants randomized to receive albuterol/budesonide Experimental Treatment 1 Intervention

Participants will be randomized based on Visit 1 FeNO levels (\< 50 ppb / ≥ 50 ppb) and geographic region. Participants who are randomized to receive albuterol/budesonide for as-needed rescue therapy will be compared to participants randomized to receive albuterol for as-needed rescue therapy.

Group II: Group 2 - Participants randomized to receive albuterol Active Control 1 Intervention

Participants will be randomized based on Visit 1 FeNO levels (\< 50 ppb / ≥ 50 ppb) and geographic region. Participants who are randomized to receive albuterol/budesonide for as-needed rescue therapy will be compared to participants randomized to receive albuterol for as-needed rescue therapy.

Albuterol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Albuterol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in European Union as Salbutamol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in Canada as Salbutamol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Who Is Running the Clinical Trial?

AstraZeneca

Lead 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

Fortrea

Industry Sponsor

Trials

22

Recruited

5,800+

Published Research Related to This Trial

In a study of 57 patients, a combination aerosol of beclomethasone dipropionate and salbutamol significantly improved lung function (measured by FEV1 and PEFR) and symptom scores compared to doubling the dose of salbutamol alone.

Patients preferred the combination treatment, indicating that using beclomethasone dipropionate alongside salbutamol offers better asthma control than simply increasing salbutamol dosage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The superiority of combination beclomethasone and salbutamol over standard dosing of salbutamol in the treatment of chronic asthma. Haahtela, T., Alanko, K., Muittari, A., et al.[2013]

In a study of 70 patients with acute bronchial asthma, the combination of budesonide and salbutamol significantly improved symptoms and pulmonary function compared to salbutamol alone, with faster relief from respiratory issues like cough and wheezing.

Patients receiving the budesonide treatment also showed lower levels of eosinophils and IgE in their blood, indicating a more effective reduction in inflammation associated with asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of budesonide combined with salbutamol on pulmonary function and peripheral blood eosinophiles and IgE in patients with acute attack of bronchial asthma. Liu, J., Wang, Y., Tang, Y., et al.[2022]

In a study of 100 children aged 1 to 12 with mild to moderate asthma exacerbations, the combination of nebulized budesonide and salbutamol significantly improved pulmonary index scores compared to salbutamol alone after 30, 60, and 90 minutes.

Patients receiving the combination treatment had a shorter duration of stay in the emergency department, with only 28% remaining after 90 minutes compared to 56% in the salbutamol-only group, indicating better overall efficacy of the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nebulized budesonide plus salbutamol and nebulized salbutamol monotherapy on mild to moderate acute exacerbation of asthma in children: A comparative study. Amir Najim Abood, HA., Al-Musawi, ZM., Hussein, AM., et al.[2022]

The combination of the long-acting inhaled beta2-agonist formoterol with the inhaled corticosteroid budesonide significantly improves lung function and reduces asthma exacerbations in both adults and children aged 4 to 17 years.

This combination therapy is safe, showing no adverse interactions between the drugs, and does not negatively affect heart rate, blood pressure, or potassium levels, although common side effects include respiratory infections and coughing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhaled budesonide/formoterol combination. McGavin, JK., Goa, KL., Jarvis, B.[2018]

In a study of 98 children with bronchial asthma, the combination of salbutamol and budesonide was found to be significantly more effective than budesonide alone, improving clinical outcomes and pulmonary function.

The combination treatment also led to a greater reduction in eosinophil levels and increased eosinophil apoptosis, suggesting enhanced immune response and inflammation control in pediatric asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salbutamol combined with budesonide in treatment of pediatric bronchial asthma and its effect on eosinophils. Li, S., Mei, Q., Qian, D., et al.[2021]

In a 4-week study involving 40 asthmatic females, using a combination inhaler of salbutamol and beclomethasone dipropionate showed similar improvements in lung function and symptoms compared to using separate inhalers with a 10-minute interval.

Both methods of administration were effective and safe, with no adverse reactions reported, suggesting that the combination inhaler is a viable option for maintenance treatment in asthma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the effects of sequential or simultaneous administration of salbutamol and beclomethasone dipropionate. Pover, GM., Greger, G., Kaspar, P.[2018]

In a study involving 3132 patients with uncontrolled moderate-to-severe asthma, the fixed-dose combination of albuterol and budesonide significantly reduced the risk of severe asthma exacerbations by 26% compared to albuterol alone.

The safety profile was similar across all treatment groups, indicating that the combination therapy is not only more effective but also safe for patients already on inhaled glucocorticoid maintenance therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Albuterol-Budesonide Fixed-Dose Combination Rescue Inhaler for Asthma. Papi, A., Chipps, BE., Beasley, R., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2504544

As-Needed Albuterol–Budesonide in Mild Asthma In this trial, as-needed use of albuterol–budesonide resulted in a lower risk of a severe asthma exacerbation than as-needed use of albuterol ...

2. astrazeneca.com astrazeneca.com/content/astraz/media-centre/press-releases/2025/statistically-significant-clinically-meaningful-batura-phase-iii-trial-provide-evidence-airsupra-standard-care-as-needed-rescue-treatment-asthma.html

Statistically significant and clinically meaningful BATURA ... The BATURA trial demonstrated treatment with Airsupra significantly reduced the risk of a severe exacerbation by 47% (5.1%, 9.1%, hazard ratio [ ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11348984/

The BATURA Study Design - PMC - PubMed Central - NIH The MANDALA study showed that this combination can significantly reduce the risk of a severe exacerbation by 28%, compared with as-needed use of ...

4. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2024/airsupra-positive-results-phase-iii-batura-trial.html

AIRSUPRA® (albuterol/budesonide) demonstrated ... The primary efficacy endpoint was the time to first severe asthma exacerbation during the study period. Secondary endpoints included severe ...

5. rethinkingasthmarescue.com rethinkingasthmarescue.com/exacerbation-study/mandala-study.html

MANDALA Exacerbation Study This prespecified exploratory analysis from MANDALA evaluated asthma deterioration and the effect of as-needed albuterol/budesonide on progression from ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1081120625003485

Albuterol–budesonide rescue inhaler for asthma Objective. To evaluate patterns of as-needed use and safety profiles of albuterol–budesonide 180/160 µg versus albuterol 180 µg, using data from ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37003355/

Albuterol-Budesonide Pressurized Metered Dose Inhaler in ... Albuterol-budesonide was well tolerated, even at regular, relatively high daily doses for 12 weeks, with no new safety findings, supporting its use as a novel ...