Evaluation of Metoprolol Tartrate in Patients with Chronic Obstructive Pulmonary Disease Without Cardiovascular Comorbidities: A Randomized Controlled Trial

The primary objective of the study titled "Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE)" is to evaluate the efficacy of **beta-blocker** treatment in patients with **chronic obstructive pulmonary disease** (COPD) who do not have co-existing cardiovascular disease. The study aims to determine whether this treatment can protect against exacerbations of COPD, cardiovascular events, and mortality. This is clinically relevant as it explores the potential benefits of beta-blockers in a population that traditionally may not receive them due to concerns about respiratory side effects, thus potentially improving patient outcomes and expanding treatment options for COPD management.

The clinical trial involves participants diagnosed with **chronic obstructive pulmonary disease** (COPD), confirmed by spirometry, and includes both male and female subjects. The study population comprises individuals aged 40 years and older, with a history of tobacco smoking or exposure to smoke, gas, or dust. Participants are required to have a sinus rhythm between 50 and 120 beats per minute at inclusion. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure that participants have no co-existing cardiovascular disease, aligning with the trial's objective to assess the effects of beta-blocker treatment on COPD exacerbations, cardiovascular events, and mortality. Written informed consent is a prerequisite for participation.

The clinical trial is designed to evaluate the efficacy of **metoprolol tartrate** in patients with **chronic obstructive pulmonary disease** (COPD) who do not have co-existing cardiovascular disease. The trial is structured as a randomized, double-blind, controlled study, ensuring that neither the participants nor the researchers know which treatment the participants are receiving, thereby minimizing bias. The trial is expected to run from May 18, 2018, to December 31, 2025, with a maximum treatment period of 12 months for each participant.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as a diagnosis of COPD confirmed by spirometry, age of 40 years or older, and sinus rhythm within specified limits. Written informed consent is also required. Following the screening, participants will be randomly assigned to receive either Seloken 100 mg or 50 mg tablets, administered orally. The primary endpoint is a composite of time to death, exacerbations of COPD, and cardiovascular events, with secondary endpoints including time to death, time to exacerbation of COPD, and time to a cardiovascular event.

Throughout the trial, participants will attend regular follow-up visits to monitor their health status and any adverse events. These visits are crucial for collecting data on the primary and secondary endpoints. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted. Participants may be withdrawn from the study early if they experience significant adverse effects, fail to comply with the study protocol, or withdraw consent. The trial aims to provide comprehensive data on the potential protective effects of beta-blocker treatment in this patient population, contributing to the understanding of COPD management.

The clinical trial involves the administration of **Seloken 100mg tablett**, which contains the active substance **metoprolol tartrate**. This medication is provided in tablet form and is intended for **oral use**. The maximum daily dose is 100 mg, with a total maximum dose of 36.5 mg over a treatment period of up to 12 months. The pharmaceutical product is manufactured by AstraZeneca AB and is classified under the ATC code C07AB02, indicating its role as a beta-blocker. The chemical origin of the active substance ensures its efficacy in the intended therapeutic context.

Additionally, the trial includes the administration of **Seloken 50 mg tablett**, also containing **metoprolol tartrate** as the active ingredient. This formulation is similarly provided in tablet form for **oral use**. The dosing regimen allows for a maximum daily intake of 100 mg, with a cumulative maximum dose of 36.5 mg over a 12-month period. Like the 100 mg formulation, this product is produced by AstraZeneca AB and shares the same ATC classification, confirming its use as a beta-blocker. Both formulations are not pediatric and are not classified as orphan drugs.

Throughout the trial, participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed regimen. The trial aims to evaluate the protective effects of beta-blocker treatment in patients with Chronic Obstructive Pulmonary Disease (COPD) without co-existing cardiovascular disease, focusing on the prevention of COPD exacerbations, cardiovascular events, and mortality.

The efficacy of the clinical trial titled "Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE)" will be assessed using both primary and secondary endpoints. The primary endpoint is a composite measure that includes time to death, exacerbations of **Chronic Obstructive Pulmonary Disease (COPD)**, and cardiovascular events such as myocardial infarction, angina pectoris, heart failure, stroke, transient ischemic attack, or cerebral hemorrhage. These events will be recorded in the Swedish National Patient Register or in electronic primary care records using specific ICD codes (I20, I21, I22, I48, I50.1-9, I61, I63, or G45.9).

Secondary endpoints include time to death (both all-cause and cause-specific), time to exacerbation of COPD, time to a cardiovascular event, and an extensive health-economic analysis. The trial aims to investigate the protective effects of beta-blocker treatment in patients with COPD who do not have co-existing cardiovascular disease. The efficacy parameters will be collected and analyzed throughout the trial duration, which is estimated to conclude by December 31, 2025. The trial involves the use of the pharmaceutical product Seloken, containing the active substance **metoprolol tartrate**, administered in tablet form.