Breztri/Trixeo for Chronic Obstructive Pulmonary Disease

(THARROS Trial)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: AstraZeneca

Must be taking: Inhaled dual/triple therapy

Disqualifiers: Asthma, Unstable disorders, Active infection, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests if a triple medication inhaler can improve heart and lung health in high-risk COPD patients better than a dual medication inhaler. Using a single inhaler with three medications has been shown to improve lung function and reduce flare-ups in COPD patients compared to using two medications, but it may increase the risk of pneumonia.

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.

What data supports the effectiveness of the drug Breztri/Trixeo for Chronic Obstructive Pulmonary Disease?

Research shows that the Trixeo Aerosphere, which includes budesonide, improves lung function and reduces exacerbation rates and mortality in COPD patients compared to other combinations. Additionally, budesonide-based therapies are associated with a lower incidence of severe pneumonia and possibly lower all-cause death rates compared to fluticasone-based therapies. ^{1 2 3 4 5}

Is budesonide-based therapy safe for humans?

Budesonide-based therapy is generally safe for humans, with studies showing it has a lower incidence of severe pneumonia and possibly lower all-cause death compared to fluticasone-based therapy in COPD patients. Additionally, it is as safe and effective as other inhalers for asthma, with no significant changes in cortisol levels, which are indicators of stress and inflammation in the body. ^{1 3 4 6 7}

What makes the drug Breztri/Trixeo unique for treating COPD?

Breztri/Trixeo is unique because it combines three medications in one inhaler: budesonide (a steroid to reduce inflammation), formoterol (a long-acting bronchodilator to help open airways), and glycopyrronium (an anticholinergic to relax airway muscles). This combination improves lung function, reduces flare-ups, and enhances quality of life more effectively than using two of these medications alone. ^{2 3 5 8 9}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Budesonide (Corticosteroid)

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.

Participant Groups

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 Canada for the following indications:

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

Findings from Research

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]

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]

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 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]

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 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]

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]

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]

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinicomorphological assessment of budesonide efficiency in patients with bronchial asthma]. [2006]

2. Belgium pubmed.ncbi.nlm.nih.gov

[Fixed combination of budesonide, formoterol, glycopyrronium for the treatment of severe COPD : Trixeo Aerosphere®]. [2022]

3. United States 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. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Fluticasone-Based versus Budesonide-Based Triple Therapies in COPD: Real-World Comparative Effectiveness and Safety. [2022]

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

Effectiveness and Patient Satisfaction with Budesonide/Formoterol Easyhaler&#174; Among Patients with Asthma or COPD Switching from Previous Treatment: a Real-World Study of Patient-Reported Outcomes. [2020]

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

Safety, tolerability and acceptability of two dry powder inhalers in the administration of budesonide in steroid-treated asthmatic patients. [2019]

7. Switzerland 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. [2017]

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

Cost-Effectiveness of Single- versus Multiple-Inhaler Triple Therapy in a UK COPD Population: The INTREPID Trial. [2022]

9. United States 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. [2022]