A Randomized Controlled Trial Comparing the Efficacy of Umeclidinium Bromide, Fluticasone Furoate, and Vilanterol Versus LABA-LAMA Combination in High-Risk COPD Patients

The primary objective of this study is to determine the efficacy of **Trelegy®** compared to LABA-LAMA treatment in improving clinical control (CC) in patients with Chronic Obstructive Pulmonary Disease (COPD) classified as GOLD B+. Clinical control is a validated composite endpoint that includes two domains: stability and impact. This objective is clinically relevant as it aims to enhance the management of COPD, potentially leading to better patient outcomes by improving disease stability and reducing its impact on patients' daily lives.

Secondary objectives include:

• Determining the efficacy of Trelegy® versus LABA-LAMA treatment in improving Clinical Important Deterioration (CID-CAT) in COPD B+ patients. This endpoint includes the occurrence of moderate/severe exacerbations, lung function decline (≥100 mL decrease from baseline in trough forced expiratory volume in 1 second (FEV1)), and deterioration in health status symptoms (≥2.0 units in COPD Assessment Test (CAT) score).
• Evaluating the impact of Trelegy® versus LABA-LAMA combination on several health status domains in COPD B+ patients.
• Determining independent predictors for permanently, intermittently, or never achieving clinical control status over the study period.

The clinical trial focuses on individuals diagnosed with **Chronic Obstructive Pulmonary Disease** (COPD), specifically targeting those with the B+ phenotype. The study population comprises both male and female participants aged between 40 and 80 years. Participants are required to be current or former smokers with a history of at least 10 pack-years. The trial does not include a vulnerable population. Participants must have a diagnosis of COPD according to the GOLD 2023 criteria, with a post-bronchodilator FEV1/FVC ratio of less than 0.7 and a post-bronchodilator FEV1 between 30% and 70% of the reference value. Additionally, they should have a COPD Assessment Test (CAT) score of 10 or higher despite being on LABA-LAMA treatment for at least three months, have experienced at least one moderate exacerbation of COPD in the previous year, and have a blood eosinophil count of 150 cells/μL or more. The sponsor has not provided the total number of participants for this trial.

The clinical trial is designed to evaluate the efficacy of **Trelegy** compared to LABA-LAMA treatment in improving clinical control in patients with **Chronic Obstructive Pulmonary Disease** (COPD). This trial is a randomized, controlled study with an open-label, pragmatic approach. The trial is expected to last until July 31, 2025, with recruitment starting on December 31, 2023. Participants will be randomly assigned to receive either Trelegy or a LABA-LAMA combination, with the primary objective being to assess the association between these treatments and clinical control at all study visits.

Participants will undergo a series of study visits, beginning with a screening visit to confirm eligibility based on criteria such as age, smoking history, and COPD diagnosis according to GOLD 2023 guidelines. The inclusion criteria specify that participants must be between 40 and 80 years old, have a history of smoking of at least 10 pack-years, and meet specific clinical and laboratory criteria related to their COPD status. The study will include follow-up visits at months 3, 6, 9, and 12 to monitor clinical control and other health status-related endpoints. The end-of-study visit will conclude the participant's involvement in the trial.

The expected duration of participant involvement is 12 months, with conditions for early termination including withdrawal of consent or adverse events that compromise participant safety. The trial will assess both primary and secondary endpoints, including the persistence of clinical control and health status comparisons between the two treatment arms. The study aims to provide insights into the effectiveness of Trelegy in maintaining clinical control and improving health outcomes in high-risk COPD patients.

The clinical trial involves the administration of **Trelegy Ellipta** as the experimental medication. Trelegy Ellipta is an inhalation powder, pre-dispensed, containing the active substances **umeclidinium bromide**, **fluticasone furoate**, and **vilanterol**. The pharmaceutical form is an inhalation powder, and it is administered via inhalation. The maximum daily dose is 92 micrograms, and the treatment period is up to 12 months. Participant compliance is monitored through regular follow-ups and adherence checks.

In addition to the experimental medication, the trial includes several comparator treatments. One such comparator is **LAVENTAIR ELLIPTA**, which is an inhalation powder, pre-dispensed, containing **umeclidinium bromide** and **vilanterol**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is also up to 12 months.

Another comparator is **ANORO ELLIPTA**, which is similar in form and administration to LAVENTAIR ELLIPTA, containing the same active substances, **umeclidinium bromide** and **vilanterol**. The dosage and treatment period are consistent with the other comparator treatments.

**Ultibro Breezhaler** is also used as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. This medication is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period extends to 12 months.

**Tovanor Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Oslif Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Ulunar Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Onbrez Breezhaler** is also used as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Spiolto Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Seebri Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Brimica Genuair** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Beglan Accuhaler** is also used as a comparator, provided as an inhalation powder containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Formoterol STADA** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Duaklir Genuair** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Gregal** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 10 micrograms, and the treatment period is up to 12 months.

**Sirkava** is another comparator, available as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Formatris Novolizer** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**FORADIL Aerolizer** is another comparator, available as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Incruse Ellipta** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Rolufta Ellipta** is another comparator, available as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Eklira Genuair** is included as a comparator, provided as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Bretaris Genuair** is another comparator, available as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Broncoral Neo** is included as a comparator, provided as a pressurised inhalation solution containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Inaspir** is another comparator, available as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Soltel** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 100 micrograms, and the treatment period is up to 12 months.

**Striverdi Respimat** is another comparator, available as an inhalation solution containing **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Yanimo Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva Respimat** is another comparator, available as an inhalation solution containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Tavulus** is another comparator, available as an inhalation powder hard capsule containing **tiotropium**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Braltus** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 10 micrograms, and the treatment period is up to 12 months.

**OXIS TURBUHALER** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 36 micrograms, and the treatment period is up to 12 months.

**Betamican** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent** is another comparator, available as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Inaspir Accuhaler** is another comparator, available as an inhalation powder, pre-dispensed, containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent Accuhaler** is included as a comparator, provided as an inhalation powder containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan Accuhaler** is another comparator, available as an inhalation powder containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Formoterol Aldo-Unión** is included as a comparator, provided as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**FORADIL Aerolizer** is another comparator, available as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Formatris Novolizer** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Broncoral Neo** is another comparator, available as a pressurised inhalation solution containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Duaklir Genuair** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Brimica Genuair** is another comparator, available as an inhalation powder containing **formoterol fumarate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Bretaris Genuair** is included as a comparator, provided as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Eklira Genuair** is another comparator, available as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Rolufta Ellipta** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Incruse Ellipta** is another comparator, available as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Ultibro Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Xoterna Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Ulunar Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Seebri Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Enurev Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Tovanor Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Hirobriz Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Oslif Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Onbrez Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Spiolto Respimat** is another comparator, available as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Yanimo Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Striverdi Respimat** is another comparator, available as an inhalation solution containing **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva** is another comparator, available as an inhalation powder hard capsule containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Tavulus** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Braltus** is another comparator, available as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 10 micrograms, and the treatment period is up to 12 months.

**OXIS TURBUHALER** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 36 micrograms, and the treatment period is up to 12 months.

**Betamican** is another comparator, available as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan** is another comparator, available as a pressurised inhalation suspension containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Inaspir Accuhaler** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent Accuhaler** is another comparator, available as an inhalation powder containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan Accuhaler** is included as a comparator, provided as an inhalation powder containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Formoterol Aldo-Unión** is another comparator, available as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**FORADIL Aerolizer** is included as a comparator, provided as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Formatris Novolizer** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Broncoral Neo** is included as a comparator, provided as a pressurised inhalation solution containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Duaklir Genuair** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Brimica Genuair** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Bretaris Genuair** is another comparator, available as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Eklira Genuair** is included as a comparator, provided as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Rolufta Ellipta** is another comparator, available as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Incruse Ellipta** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Ultibro Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Xoterna Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Ulunar Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Seebri Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Enurev Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Tovanor Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Hirobriz Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Oslif Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Onbrez Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Spiolto Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Yanimo Respimat** is another comparator, available as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Striverdi Respimat** is included as a comparator, provided as an inhalation solution containing **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva Respimat** is another comparator, available as an inhalation solution containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Tavulus** is another comparator, available as an inhalation powder hard capsule containing **tiotropium**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Braltus** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 10 micrograms, and the treatment period is up to 12 months.

**OXIS TURBUHALER** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 36 micrograms, and the treatment period is up to 12 months.

**Betamican** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent** is another comparator, available as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Inaspir Accuhaler** is another comparator, available as an inhalation powder, pre-dispensed, containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent Accuhaler** is included as a comparator, provided as an inhalation powder containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan Accuhaler** is another comparator, available as an inhalation powder containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Formoterol Aldo-Unión** is included as a comparator, provided as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**FORADIL Aerolizer** is another comparator, available as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Formatris Novolizer** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Broncoral Neo** is another comparator, available as a pressurised inhalation solution containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Duaklir Genuair** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Brimica Genuair** is another comparator, available as an inhalation powder containing **formoterol fumarate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Bretaris Genuair** is included as a comparator, provided as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Eklira Genuair** is another comparator, available as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Rolufta Ellipta** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Incruse Ellipta** is another comparator, available as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Ultibro Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Xoterna Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Ulunar Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Seebri Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Enurev Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Tovanor Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Hirobriz Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Oslif Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Onbrez Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Spiolto Respimat** is another comparator, available as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Yanimo Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Striverdi Respimat** is another comparator, available as an inhalation solution containing **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva** is another comparator, available as an inhalation powder hard capsule containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Tavulus** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Braltus** is another comparator, available as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 10 micrograms, and the treatment period is up to 12 months.

**OXIS TURBUHALER** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 36 micrograms, and the treatment period is up to 12 months.

**Betamican** is another comparator, available as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan** is another comparator, available as a pressurised inhalation suspension containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Inaspir Accuhaler** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent Accuhaler** is another comparator, available as an inhalation powder containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan Accuhaler** is included as a comparator, provided as an inhalation powder containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Formoterol Aldo-Unión** is another comparator, available as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**FORADIL Aerolizer** is included as a comparator, provided as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Formatris Novolizer** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Broncoral Neo** is included as a comparator, provided as a pressurised inhalation solution containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Duaklir Genuair** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Brimica Genuair** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Bretaris Genuair** is another comparator, available as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Eklira Genuair** is included as a comparator, provided as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Rolufta Ellipta** is another comparator, available as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Incruse Ellipta** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Ultibro Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Xoterna Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Ulunar Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Seebri Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Enurev Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Tovanor Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Hirobriz Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Oslif Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Onbrez Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Spiolto Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Yanimo Respimat** is another comparator, available as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Striverdi Respimat** is included as a comparator, provided as an inhalation solution containing **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva Respimat** is another comparator, available as an inhalation solution containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Tavulus** is another comparator, available as an inhalation powder hard capsule containing **tiotropium**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Braltus** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 10 micrograms, and the treatment period is up to 12 months.

**OXIS TURBUHALER** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 36 micrograms, and the treatment period is up to 12 months.

**Betamican** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent** is another comparator, available as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Inaspir Accuhaler** is another comparator, available as an inhalation powder, pre-dispensed, containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent Accuhaler** is included as a comparator, provided as an inhalation powder containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan Accuhaler** is another comparator, available as an inhalation powder containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Formoterol Aldo-Unión** is included as a comparator, provided as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**FORADIL Aerolizer** is another comparator, available as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Formatris Novolizer** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Broncoral Neo** is another comparator, available as a pressurised inhalation solution containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Duaklir Genuair** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Brimica Genuair** is another comparator, available as an inhalation powder containing **formoterol fumarate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Bretaris Genuair** is included as a comparator, provided as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Eklira Genuair** is another comparator, available as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Rolufta Ellipta** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Incruse Ellipta** is another comparator, available as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Ultibro Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Xoterna Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Ulunar Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Seebri Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Enurev Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Tovanor Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Hirobriz Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Oslif Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Onbrez Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Spiolto Respimat** is another comparator, available as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Yanimo Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Striverdi Respimat** is another comparator, available as an inhalation solution containing **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva** is another comparator, available as an inhalation powder hard capsule containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Tavulus** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Braltus** is another comparator, available as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of 10 micrograms, and the treatment period is up to 12 months.

**OXIS TURBUHALER** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 36 micrograms, and the treatment period is up to 12 months.

**Betamican** is another comparator, available as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent** is included as a comparator, provided as a pressurised inhalation suspension containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan** is another comparator, available as a pressurised inhalation suspension containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Inaspir Accuhaler** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Serevent Accuhaler** is another comparator, available as an inhalation powder containing **salmeterol**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Beglan Accuhaler** is included as a comparator, provided as an inhalation powder containing **salmeterol xinafoate**. It is administered via inhalation with a maximum daily dose of 200 micrograms, and the treatment period is up to 12 months.

**Formoterol Aldo-Unión** is another comparator, available as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**FORADIL Aerolizer** is included as a comparator, provided as an inhalation powder hard capsule containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Formatris Novolizer** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Broncoral Neo** is included as a comparator, provided as a pressurised inhalation solution containing **formoterol fumarate dihydrate**. It is administered via inhalation with a maximum daily dose of 48 micrograms, and the treatment period is up to 12 months.

**Duaklir Genuair** is another comparator, available as an inhalation powder containing **formoterol fumarate dihydrate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Brimica Genuair** is included as a comparator, provided as an inhalation powder containing **formoterol fumarate** and **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 680 micrograms, and the treatment period is up to 12 months.

**Bretaris Genuair** is another comparator, available as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Eklira Genuair** is included as a comparator, provided as an inhalation powder containing **aclidinium bromide**. It is administered via inhalation with a maximum daily dose of 644 micrograms, and the treatment period is up to 12 months.

**Rolufta Ellipta** is another comparator, available as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Incruse Ellipta** is included as a comparator, provided as an inhalation powder, pre-dispensed, containing **umeclidinium bromide**. It is administered via inhalation with a maximum daily dose of 55 micrograms, and the treatment period is up to 12 months.

**Ultibro Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Xoterna Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Ulunar Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide** and **indacaterol maleate**. It is administered via inhalation with a maximum daily dose of 85 micrograms, and the treatment period is up to 12 months.

**Seebri Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Enurev Breezhaler** is another comparator, available as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Tovanor Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **glycopyrronium bromide**. It is administered via inhalation with a maximum daily dose of 44 micrograms, and the treatment period is up to 12 months.

**Hirobriz Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Oslif Breezhaler** is included as a comparator, provided as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Onbrez Breezhaler** is another comparator, available as inhalation powder hard capsules containing **indacaterol**. It is administered via inhalation with a maximum daily dose of 300 micrograms, and the treatment period is up to 12 months.

**Spiolto Respimat** is included as a comparator, provided as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Yanimo Respimat** is another comparator, available as an inhalation solution containing **tiotropium** and **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Striverdi Respimat** is included as a comparator, provided as an inhalation solution containing **olodaterol**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva Respimat** is another comparator, available as an inhalation solution containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 5 micrograms, and the treatment period is up to 12 months.

**Spiriva** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide monohydrate**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Tavulus** is another comparator, available as an inhalation powder hard capsule containing **tiotropium**. It is administered via inhalation with a maximum daily dose of 18 micrograms, and the treatment period is up to 12 months.

**Braltus** is included as a comparator, provided as an inhalation powder hard capsule containing **tiotropium bromide**. It is administered via inhalation with a maximum daily dose of

The efficacy of the clinical trial will be assessed by evaluating the improvement in clinical control (CC) in patients with Chronic Obstructive Pulmonary Disease (COPD) B+ phenotype. The primary endpoint is to determine the association between the use of Trelegy® versus LABA-LAMA treatment and the persistence of clinical control at all study visits, specifically at months 3, 6, 9, and 12. This will be measured using a validated composite endpoint that includes two domains: stability and impact.

Secondary endpoints include assessing the association between the treatments and persistent non-deterioration by CID-CAT at all study visits, as well as comparing several health status-related endpoints between the study arms. These endpoints will evaluate the stability domain, which includes general status since the last visit and exacerbations in the last 3 months, and the impact domain, which includes sputum color, rescue medication use, minutes walked per day, and **dyspnea** (mMRC). Additional assessments will include time to first non-achievement event for both CC and CID-CAT, annual FEV1 and FVC changes, and the mean and annual rate of moderate and severe exacerbations (ECOPD).

The efficacy parameters will be collected and analyzed at specified timepoints throughout the study duration, ensuring a comprehensive evaluation of the treatment effects on the clinical control of COPD in the study population.