Inhaled Steroid + Beta Agonist for Pneumonia

(ARREST Trial)

Recruiting at 14 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

600 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This research study seeks to establish the effectiveness of a combination of an inhaled corticosteroid and a beta agonist compared to placebo for the prevention of acute respiratory failure (ARF) in hospitalized patients with pneumonia and hypoxemia.

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 the combination of inhaled budesonide and formoterol safe for humans?

Research shows that the combination of inhaled budesonide and formoterol, used in treatments like Symbicort, is generally safe for humans, as it has been tested in various studies for conditions like asthma and chronic obstructive pulmonary disease (COPD). ^{1 2 3 4 5}

How is the drug budesonide/formoterol unique for treating pneumonia?

Budesonide/formoterol is unique because it combines an inhaled steroid and a long-acting beta agonist in a dry powder inhaler, which is designed to be easy to use and minimize common inhaler errors, potentially offering more consistent dose delivery compared to other inhalers. ^{1 2 3 4 6}

What data supports the effectiveness of the drug Inhaled budesonide and formoterol for pneumonia?

The combination of budesonide and formoterol is effective in managing asthma and chronic obstructive pulmonary disease (COPD) by improving inhaler technique and ensuring consistent dose delivery, which suggests potential benefits for respiratory conditions like pneumonia. ^{1 2 3 4 6}

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

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]

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]

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]

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/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 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]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Bioequivalence of budesonide plus formoterol (BF) Spiromax® and BF Turbohaler® (with and without charcoal block) in healthy volunteers. [2015]

2. England 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. [2019]

3. England 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. [2018]

4. United States 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. [2015]

5. England 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. [2019]

6. New Zealand 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. [2019]