Inhaled Steroid + Beta Agonist for Pneumonia

(ARREST Trial)

No longer recruiting at 15 trial locations

Overseen By Joseph Levitt, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stanford University

Must not be taking: Inhaled corticosteroids, Beta-agonists, Systemic steroids

Disqualifiers: Chronic lung disease, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two inhaled medications—budesonide and formoterol (an inhaled steroid and beta agonist)—to determine if they can prevent serious lung problems in hospitalized patients with severe pneumonia. Participants will receive either this combination treatment or a placebo (a saltwater solution with no active medication) for comparison. The trial targets those hospitalized with severe pneumonia who require extra oxygen during the day due to low blood oxygen levels. The goal is to see if this treatment can prevent the condition from worsening and causing acute respiratory failure. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on inhaled corticosteroids or beta-agonists for a condition, you may need to stop them to participate.

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

Research shows that using inhaled budesonide and formoterol together is generally safe. Studies have found that this combination works well for treating asthma. In one study, participants using these medications experienced fewer asthma attacks and needed their rescue inhalers less often.

Another study demonstrated that this combination is as effective as other treatments and has a good safety record. Most participants in these studies experienced only mild side effects, such as throat irritation and cough, with serious problems being rare.

Since this treatment is already approved for asthma, its safety for that condition is well-known. This suggests it might also be safe for other uses, such as in this trial for pneumonia. However, the ongoing research will confirm its specific safety for pneumonia patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard of care for pneumonia, which often involves oral or intravenous antibiotics, the treatment of inhaled budesonide and formoterol is administered directly to the lungs via inhalation. Researchers are excited about these treatments because they offer a targeted approach that could reduce inflammation and open airways more effectively by delivering medication straight to the respiratory tract. This method has the potential to act faster and with fewer systemic side effects, providing an innovative alternative to traditional pneumonia treatments.

What evidence suggests that inhaled budesonide and formoterol could be effective for pneumonia?

Research has shown that inhaled budesonide and formoterol, which participants in this trial may receive, effectively manage breathing problems like asthma and COPD (chronic obstructive pulmonary disease). Studies have found that these medications improve lung function and control symptoms. Many patients report high satisfaction with this combination, noting better management of their conditions. The combination reduces lung swelling and relaxes the muscles around the airways, making breathing easier. While mainly used for asthma, research suggests it might also help prevent severe breathing issues in pneumonia patients by keeping airways open and reducing lung swelling. ^{1 3 5 6 7}

Who Is on the Research Team?

Emir Festic, MD

Principal Investigator

Mayo Clinic

Joseph Levitt, MD, MS

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

Adults hospitalized with severe pneumonia and low oxygen levels who need supplemental oxygen or non-invasive ventilation can join. Excluded are those already intubated, on chronic steroids or inhaled medications for lung conditions, allergic to trial drugs, severely ill with a life expectancy under 48 hours, pregnant women, prisoners, and patients with certain heart issues.

Inclusion Criteria

I am 18 or older, hospitalized with severe pneumonia, need extra oxygen, and might have an infection.

I was admitted for pneumonia without severe low oxygen levels but can be observed for 24 hours.

Exclusion Criteria

I need daytime oxygen or a ventilator, not just for sleep apnea or obesity breathing issues.

I am COVID-19 positive and taking more than 6 mg of dexamethasone.

I use inhaled corticosteroids or beta-agonists for my condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive either aerosolized formoterol and budesonide or placebo every 12 hours for 10 doses

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Inhaled budesonide and formoterol
• Inhaled placebo

Trial Overview The study is testing if inhaling a mix of budesonide (a steroid) and formoterol (a beta agonist) can prevent acute respiratory failure in pneumonia patients compared to an inactive placebo. Participants will be randomly assigned to receive either the drug combination or placebo.

How Is the Trial Designed?

Group I: Intervention Active Control 1 Intervention

aerosolized formoterol (20 mcg/2 ml) and budesonide (1.0 mg/2 ml) every 12 hours x 10 doses

Group II: Placebo Placebo Group 1 Intervention

4 ml aerosolized 0.9% saline every 12 hours x 10 doses

Inhaled budesonide and formoterol is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Symbicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)

Approved in United States as Symbicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)

Approved in Canada as Symbicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)

Approved in Japan as Symbicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study involving 493 asthma patients, those using the DuoResp® Spiromax® inhaler achieved mastery of inhaler technique more effectively (94%) compared to those using the Symbicort® Turbuhaler® (87%), indicating that Spiromax may be easier to use.

While both inhalers improved asthma control, the long-term maintenance of inhaler mastery after 12 weeks was similar for both devices; however, an independent expert review showed that patients using Spiromax had significantly higher verified mastery levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of inhaler technique and achievement and maintenance of mastery of budesonide/formoterol Spiromax® compared with budesonide/formoterol Turbuhaler® in adult patients with asthma: the Easy Low Instruction Over Time (ELIOT) study. Price, DB., Thomas, V., Richard Dekhuijzen, PN., et al.[2019]

In a study of 373 patients with moderate persistent asthma, Symbicort (budesonide/formoterol) significantly improved lung function compared to fluticasone propionate, with greater increases in morning peak expiratory flow (PEF) and fewer asthma exacerbations.

Symbicort also led to better overall asthma control, as indicated by a higher percentage of symptom-free days and reduced reliance on reliever medication, while both treatments were well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination therapy with single inhaler budesonide/formoterol compared with high dose of fluticasone propionate alone in patients with moderate persistent asthma. Bateman, ED., Bantje, TA., João Gomes, M., et al.[2019]

Budesonide formoterol (BF) Spiromax® is pharmacokinetically equivalent to BF Turbohaler®, as demonstrated in two studies with 90 healthy volunteers each, showing similar absorption and peak drug concentrations for both inhalers.

Both inhalers were well tolerated, with only a few minor treatment-emergent adverse events reported, indicating that BF Spiromax is a safe alternative to BF Turbohaler.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of budesonide plus formoterol (BF) Spiromax® and BF Turbohaler® (with and without charcoal block) in healthy volunteers. Weisfeld, L., Shu, Y., Shah, TP.[2015]

Budesonide/formoterol (BF) Spiromax is non-inferior to the BF Turbuhaler inhaler for disease control in patients with asthma and COPD, based on a study of 1,476 patients (385 switchers and 1,091 non-switchers).

Patients with asthma who switched to BF Spiromax experienced fewer exacerbations, reduced use of short-acting β2-agonists (SABA), and improved treatment stability compared to those who continued with BF Turbuhaler.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness evaluation of budesonide/formoterol Spiromax for the management of asthma and chronic obstructive pulmonary disease in the UK. Voorham, J., Roche, N., Benhaddi, H., et al.[2019]

In a study involving 75 prepubescent children with asthma, the growth rates of lower legs were not significantly different between the inhaled corticosteroid budesonide and long-acting β2-agonist formoterol delivered via the Spiromax inhaler and the Symbicort Turbohaler, but non-inferiority could not be established.

Both inhalers showed a negative impact on lower leg growth compared to placebo, with the Spiromax showing a growth rate difference of -0.20 mm/week and the Symbicort showing -0.118 mm/week, indicating that further research is needed to fully understand their effects on growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of Short-Term Growth During Treatment with Two Dry Powder Combinations of Inhaled Corticosteroids and Long-Acting β₂-Agonists. Wolthers, OD., Shah, T.[2015]

Budesonide and formoterol Spiromax demonstrated non-inferiority to the Turbuhaler in improving morning peak expiratory flow (PEF) in patients with asthma over a 12-week period, indicating it is an effective alternative inhaler.

Patients showed a preference for the Spiromax device over the Turbuhaler, reporting better performance satisfaction and a willingness to continue using it, while both inhalers were well tolerated with no significant differences in adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blinded, double-dummy efficacy and safety study of budesonide-formoterol Spiromax® compared to budesonide-formoterol Turbuhaler® in adults and adolescents with persistent asthma. Virchow, JC., Rodriguez-Roisin, R., Papi, A., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6224753/

Real-world effectiveness evaluation of budesonide ... Among UK patients with asthma and COPD, real-world use of BF Spiromax was non-inferior to BF Turbuhaler in terms of disease control.

2. publications.ersnet.org publications.ersnet.org/content/erj/48/suppl60/pa627

Real-life effectiveness of budesonide/formoterol for the ... ConclusionThese preliminary results suggest that switching from other FDC inhalers to DRS Spiromax® was either due to poor disease control, or to improve ( ...

3. karger.com karger.com/res/article/97/4/292/290787/Patient-Satisfaction-and-Clinical-Outcomes-with

Patient Satisfaction and Clinical Outcomes with ... At baseline, 60.1% of patients were “satisfied” or “very satisfied” with their previous inhaler, and this increased to 88.8% at week 12 of B/F ...

4. ema.europa.eu ema.europa.eu/en/documents/variation-report/biresp-spiromax-h-c-3890-ii-0033-epar-assessment-report-variation_en.pdf

BiResp Spiromax, INN-budesonide and formoterol ... - EMA Asthma: BiResp Spiromax is indicated in the regular treatment of asthma, where use of a combination. (inhaled corticosteroid and long-acting β2 ...

5. semanticscholar.org semanticscholar.org/paper/A-randomized%2C-double-blinded%2C-double-dummy-efficacy-Virchow-Rodr%C3%ADguez-Rois%C3%ADn/5df3705ff15d590e3b82da66f634c157c1f51c8a

A randomized, double-blinded, double-dummy efficacy and ... This study demonstrates the non-inferiority of BF Spiromax vs BF Turbuhaler in patients (≥12 years) with asthma, and more patients preferred the Spiromx ...

6. bmcpulmmed.biomedcentral.com bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-016-0200-x

A randomized, double-blinded, double-dummy efficacy and ... A randomized, double-blinded, double-dummy efficacy and safety study of budesonide–formoterol Spiromax® compared to budesonide–formoterol ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01803555

Efficacy and Safety Evaluation of Budesonide/Formoterol ... The primary objective of the study is to establish whether budesonide/formoterol fumarate dihydrate (BF) Spiromax 160/4.5 micrograms (mcg) is as effective ...