Breztri/Trixeo for Chronic Obstructive Pulmonary Disease

(THARROS Trial)

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AstraZeneca

Must be taking: Inhaled dual/triple therapy

Disqualifiers: Asthma, Unstable disorders, Active infection, others

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

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

1060 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination treatment of three drugs, including Breztri/Trixeo, can improve heart and lung health in people with Chronic Obstructive Pulmonary Disease (COPD) compared to a two-drug treatment. The main focus is on improving outcomes for those at high risk for heart and lung issues. It suits individuals who have had COPD for at least a year, frequently experience worsening symptoms, and have a history of smoking. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment for COPD.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should have been on a stable dose of inhaled dual or triple therapy for at least 3 months before joining the study, which suggests you may need to continue your current COPD medications.

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

Research shows that the combination of budesonide, glycopyrronium, and formoterol (BGF) is safe and well-tolerated for people with COPD (Chronic Obstructive Pulmonary Disease). Studies have found that this treatment effectively improves lung function and manages symptoms. Side effects are usually mild, such as throat irritation or headaches, and resemble those from other inhaled treatments.

Research also indicates that the glycopyrronium and formoterol combination is safe for long-term use. Most side effects are mild, like dry mouth or cough. Studies confirm that it improves lung function and reduces COPD flare-ups.

Both treatments have been tested in people with moderate to severe COPD, making them reliable options. For those considering joining a trial, these findings suggest that the treatments are generally safe, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer a novel combination of medications for managing Chronic Obstructive Pulmonary Disease (COPD). The investigational treatment, which combines Budesonide, Glycopyrronium, and Formoterol Fumarate (BGF MDI), is unique because it integrates a corticosteroid (Budesonide) with two bronchodilators in one inhaler. This triple-action approach could enhance lung function and reduce inflammation more effectively than current standard therapies, which typically involve separate inhalers or dual therapies. Additionally, the BGF MDI's specific formulation aims to provide a convenient, all-in-one treatment option that might improve patient adherence and outcomes.

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

Research shows that a combination of three medications—budesonide, glycopyrronium, and formoterol fumarate (BGF)—can improve the health of people with Chronic Obstructive Pulmonary Disease (COPD). Studies have found that BGF significantly enhances patients' daily lives, as measured by specific health surveys. Additionally, BGF has been linked to a lower risk of death from any cause, potentially helping people live longer. In this trial, participants may receive either BGF or another treatment option, glycopyrronium and formoterol fumarate (GFF), which is also effective and well-tolerated. Research shows GFF works as well as other treatments. Both options are promising for managing COPD, but BGF might offer more benefits because it includes budesonide. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people with COPD who are at high risk of heart and lung complications. Participants should have a history of exacerbations or evidence of heart disease. They must not be currently experiencing a flare-up or have other significant health issues that could interfere with the study.

Inclusion Criteria

Are you HIV+?

Do you have asthma?

Do you have high blood pressure?

Exclusion Criteria

I had a severe COPD flare-up treated with steroids or antibiotics, or I was hospitalized for it within the last 2 weeks.

Active vaping of any products or using smoked marijuana within the 6 months prior to randomization and during the study

I have a significant lung condition that is not COPD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either BGF MDI 320/14.4/9.6 μg or GFF MDI 14.4/9.6 μg to assess cardiopulmonary outcomes

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Budesonide

Trial Overview The study tests if Breztri/Trixeo, which combines three types of medication (ICS/LAMA/LABA), can improve heart and lung outcomes better than Bevespi, which combines two medications (LAMA/LABA) in those with COPD at high cardiopulmonary risk.

How Is the Trial Designed?

Group I: Glycopyrronium and Formoterol Fumarate Experimental Treatment 0 Interventions

GFF MDI 14.4/9.6 μg

Group II: Budesonide, Glycopyrronium, and Formoterol Fumarate Experimental Treatment 1 Intervention

BGF MDI 320/14.4/9.6 μg

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

Approved in European Union as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Crohn's disease
• Ulcerative colitis
• Microscopic colitis
• Eosinophilic esophagitis
• Primary immunoglobulin A nephropathy

Approved in United States as Entocort EC for:

• Crohn's disease
• Ulcerative colitis
• Primary immunoglobulin A nephropathy
• Eosinophilic esophagitis

Approved in Canada as Pulmicort for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis

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

Published Research Related to This Trial

In a real-world study involving 961 patients with asthma and COPD, switching to the budesonide/formoterol fumarate (B/F) Easyhaler® resulted in significant improvements in symptoms, disease control, health-related quality of life, and lung function after 12 weeks.

Patients reported increased satisfaction with the B/F Easyhaler compared to their previous inhalers, suggesting it may be a more effective treatment option for those struggling with disease control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Patient Satisfaction with Budesonide/Formoterol Easyhaler® Among Patients with Asthma or COPD Switching from Previous Treatment: a Real-World Study of Patient-Reported Outcomes. Gálffy, G., Szilasi, M., Tamási, L.[2020]

In a study involving 159 adults with moderate-to-severe asthma, budesonide delivered via an inhaler significantly reduced the need for oral glucocorticosteroids (GCSs) by 79-83% compared to only 27% in the placebo group, indicating its efficacy in managing asthma while minimizing systemic steroid use.

Approximately two-thirds of participants using budesonide were able to completely stop oral corticosteroids, and they also experienced improvements in lung function and asthma symptoms, suggesting that budesonide not only spares oral GCSs but also maintains or enhances asthma control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral glucocorticosteroid-sparing effect of budesonide administered by Turbuhaler: a double-blind, placebo-controlled study in adults with moderate-to-severe chronic asthma. Pulmicort Turbuhaler Study Group. Nelson, HS., Bernstein, IL., Fink, J., et al.[2019]

In a study involving 315 asthmatic patients over 12 weeks, the budesonide Novolizer was found to be at least as effective as the Pulmicort Turbuhaler in improving lung function (measured by FEV1), with a statistically significant difference (p < 0.001).

Both inhaler devices showed similar safety profiles, with no significant differences in adverse events or other safety measures, indicating that either device can be safely used for long-term asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical equivalence trial on budesonide delivered either by the Novolizer multidose dry powder inhaler or the Turbuhaler in asthmatic patients. Chuchalin, AG., Kremer, HJ., Metzenauer, P., et al.[2017]

In a study involving 161 adult asthmatic patients, both the Easyhaler and Turbuhaler inhalers delivered budesonide safely, with no significant changes in morning serum cortisol levels, indicating similar systemic safety profiles.

Patients found the Easyhaler to be more acceptable compared to the Turbuhaler, while both devices showed comparable efficacy in managing asthma symptoms at a dosage of 800 microg per day.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients. Tukiainen, H., Rytilä, P., Hämäläinen, KM., et al.[2019]

Budesonide, an inhalation glucocorticosteroid, significantly improved asthma symptoms in 20 patients, showing a response by the end of the first week of treatment, with a notable reduction in acute asthma episodes and decreased reliance on short-acting beta 2-agonists.

After 12 months of treatment, budesonide improved lung function, as indicated by a 31% reduction in peak expiratory velocity variability, but did not fully normalize the bronchial mucosa, suggesting that longer treatment may be necessary for complete recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinicomorphological assessment of budesonide efficiency in patients with bronchial asthma]. Budkova, AA., Volkova, LI., Budkov, SR., et al.[2006]

In a study of 39,362 COPD patients using either budesonide-based or fluticasone-based triple therapy, budesonide was found to be as effective as fluticasone in reducing exacerbations of the disease.

Budesonide-based therapy was associated with a lower risk of severe pneumonia (HR 0.84) and a reduced incidence of all-cause death (HR 0.80) among patients without prior exacerbations, suggesting it may be a safer option for certain patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluticasone-Based versus Budesonide-Based Triple Therapies in COPD: Real-World Comparative Effectiveness and Safety. Suissa, S., Dell'Aniello, S., Ernst, P.[2022]

Trixeo Aerosphere®, a new inhaled combination treatment for severe COPD, significantly improves lung function (FEV1) compared to a budesonide/formoterol combination.

This triple therapy not only reduces the rate of exacerbations and improves quality of life but also lowers mortality rates, especially in patients with higher blood eosinophil counts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Fixed combination of budesonide, formoterol, glycopyrronium for the treatment of severe COPD : Trixeo Aerosphere®]. Louis, R., Bonhomme, O., Heinen, V., et al.[2022]

The 24-week INTREPID trial showed that once-daily single-inhaler triple therapy (FF/UMEC/VI) for COPD patients provided significant clinical benefits compared to multiple-inhaler triple therapy, leading to improved lung function and quality of life.

From a UK NHS perspective, FF/UMEC/VI not only resulted in better health outcomes, providing an additional 0.253 quality-adjusted life years (QALYs), but also saved £1764 per patient, making it a cost-effective treatment option for symptomatic COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Single- versus Multiple-Inhaler Triple Therapy in a UK COPD Population: The INTREPID Trial. Halpin, DMG., Kendall, R., Shukla, S., et al.[2022]

In a study of 120 patients with acute respiratory distress syndrome (ARDS), the use of Breztri Aerosphere significantly improved clinical outcomes compared to conventional treatment, as indicated by lower APACHE II and Murray lung injury scores.

Patients treated with Breztri Aerosphere experienced shorter mechanical ventilation and ICU stays, along with improved blood gas levels and reduced inflammatory markers, suggesting its efficacy in managing ARDS through inflammation reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Efficacy of Budesonide/Glycopyrronium Bromide/Formoterol in the Treatment of Patients with Acute Respiratory Distress Syndrome and Its Effect on Inflammatory Factors. Liu, H., Wang, Z., Ren, L., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40513294/

EBISU study Triple therapy with a BGF MDI significantly improved CAT and SGRQ scores over 12 weeks. BGF MDI could be a suitable option for patients living with COPD.

2. sciencedirect.com sciencedirect.com/science/article/pii/S2212534525000711

Real-world effectiveness of budesonide/glycopyrronium/ ... Triple therapy with a BGF MDI significantly improved CAT and SGRQ scores over 12 weeks. BGF MDI could be a suitable option for patients living with COPD.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06321731?term=BUDESONIDE%20AND%20FORMOTEROL%20AND%20GLYCOPYRRONIUM&rank=7

Real-World Outcomes in COPD Patients Starting Trixeo ... The aim of the ORESTES study is to describe the characteristics of the COPD patients initiating Trixeo (BGF - budesonide / glycopyrronium / formoterol ) in ...

4. link.springer.com link.springer.com/article/10.1007/s12325-025-03361-x

Real-World Outcomes in Patients with COPD Initiating ... Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease. a ...

5. tandfonline.com tandfonline.com/doi/full/10.1080/24745332.2023.2289890

Cost-effectiveness of triple therapy with budesonide ... BGF is associated with both cost-savings and improved health benefits compared with dual therapies for maintenance treatment of COPD patients at risk of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12579692/

Real-World Outcomes in Patients with COPD Initiating ... The observed improvements, despite advanced disease, raise the possibility that earlier initiation of BGF may help optimize outcomes; however, ...

7. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(25)00334-7/fulltext

Safety of budesonide/glycopyrronium/formoterol fumarate ... This study assessed the safety of a near-zero GWP propellant, hydrofluoroolefin-1234ze (HFO-1234ze), compared with HFA-134a when used in the ...

8. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2025/Breztri-met-primary-endpoints-in-kalos-and-logos-phase-III-trials-in-asthma.html

BREZTRI met primary endpoints in KALOS and LOGOS ... The trials evaluated the efficacy and safety of BREZTRI versus maintenance treatment with ICS/LABA in adults and adolescents with uncontrolled asthma.

9. publications.ersnet.org publications.ersnet.org/content/erj/64/suppl68/pa2999

Real-world safety of budesonide/glycopyrrolate/formoterol in ... Budesonide/glycopyrronium/formoterol (BGF) is a triple therapy delivered in a metered dose inhaler (MDI) for chronic obstructive pulmonary disease (COPD).