Evaluation of Intravenous Metoprolol Tartrate Efficacy in Acute Respiratory Distress Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this randomized, double-blind, placebo-controlled clinical trial is to evaluate the efficacy of intravenous **metoprolol** in patients with **Acute Respiratory Distress Syndrome (ARDS)**. The main focus is on assessing the number of days patients are alive and free of invasive mechanical ventilation during the first 28 days. This outcome is clinically relevant as it directly impacts patient survival and quality of life by potentially reducing the duration of mechanical ventilation, which is associated with various complications.

Secondary objectives include:

• All-cause death at day 28 after randomization, measuring the cumulative incidence of death from any cause.
• Ventilator-free days at 28 days, indicating the number of days without mechanical ventilation during the first 28 days.
• Intensive care unit days of admission, assessing the number of days admitted to the intensive care unit over a 3-month period.
• Quality of life score at 3 months, evaluated using the Short Form 36 Health Survey Questionnaire (SF-36), which measures eight domains of health status.
• Arterial oxygenation on day 8, determined by mean arterial oxygen saturation (PaO2/FiO2).
• Change in arterial oxygenation over 8 days, calculated as the mean difference in arterial oxygen saturation (PaO2/FiO2) between baseline and day 8.

The clinical trial focuses on **Acute Respiratory Distress Syndrome (ARDS)** and includes participants aged 18 to 79 years. Both male and female subjects are eligible for the study, and the trial does not specifically target a vulnerable population. Participants are selected based on a clinical diagnosis of ARDS from various causes, such as pneumonia, including SARS-CoV-2, sepsis, pancreatitis, bronchospasm, and trauma, and must be admitted to the ICU. The study population is required to have undergone orotracheal intubation and mechanical ventilation within 72 hours prior to randomization. The trial does not provide specific information on the total number of participants or detailed lifestyle considerations. The sponsor has not disclosed the total number of participants involved in the study.

The clinical trial is a **randomized**, **double-blind**, placebo-controlled study designed to evaluate the efficacy of intravenous **metoprolol** in patients with **Acute Respiratory Distress Syndrome (ARDS)**. The trial aims to assess the primary endpoint of days alive and free of invasive mechanical ventilation during the first 28 days, utilizing a hierarchical composite outcome approach. The study is set to commence recruitment on November 1, 2023, and is estimated to conclude by December 1, 2027. Participants will be randomly assigned to receive either the active treatment, **Beloken 1 mg/ml solution for injection**, or a placebo, with the intervention administered parenterally.

The trial will include an initial screening visit to confirm eligibility based on criteria such as age (18-79 years), clinical diagnosis of ARDS, and specific physiological parameters. Following randomization, participants will undergo regular follow-up visits to monitor their health status, adherence to the treatment protocol, and any adverse events. The end-of-study visit will occur at the conclusion of the 28-day treatment period, where final assessments will be conducted to evaluate the primary and secondary endpoints, including all-cause mortality, ventilator-free days, and quality of life scores.

Participant involvement is expected to last for the duration of the 28-day treatment period, with additional follow-up assessments extending up to three months post-randomization. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or the occurrence of serious adverse events that compromise participant safety. The trial is conducted in compliance with ethical standards and regulatory requirements, ensuring the integrity and scientific validity of the research findings.

The clinical trial involves the administration of **metoprolol tartrate**, marketed under the name Beloken 1 mg/ml solución inyectable. This experimental medication is provided in the form of a **solution for injection**. The pharmaceutical form is specifically designed for **parenteral** administration. The dosage regimen for this trial stipulates a maximum daily dose of 15 mg, with the total dose not exceeding 15 mg over the course of the treatment period. The maximum treatment period is defined as one day. The active substance, metoprolol tartrate, is of chemical origin and is classified under the ATC code C07AB02, which corresponds to the beta-blocker category. The product is manufactured by Recordati Industria Chimica e Farmaceutica S.P.A.

In this randomized, double-blind, placebo-controlled clinical trial, the efficacy of intravenous metoprolol is being evaluated in patients with **Acute Respiratory Distress Syndrome (ARDS)**. The primary objective is to assess the number of days patients are alive and free of invasive mechanical ventilation during the first 28 days. The trial employs a hierarchical composite outcome measure, specifically the "Alive and ventilator-free days at 28 days" using a win ratio approach. The study design includes a placebo group to serve as a comparator, ensuring the reliability and validity of the trial outcomes. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol.

The efficacy of intravenous **metoprolol** in patients with Acute Respiratory Distress Syndrome (ARDS) will be assessed in a randomized, double-blind, placebo-controlled clinical trial. The primary endpoint for evaluating efficacy is the number of days patients are alive and free of invasive mechanical ventilation during the first 28 days, utilizing a hierarchical composite outcome approach known as the "win ratio." This primary endpoint will be measured over a 28-day time frame.

Secondary endpoints include the cumulative incidence of all-cause death at day 28 post-randomization, the number of ventilator-free days within the first 28 days, and the number of days admitted to the intensive care unit over a 3-month period. Additionally, the trial will assess the quality of life score at 3 months using "The Short Form 36 Health Survey Questionnaire" (SF-36), which evaluates eight domains of health status. Arterial oxygenation will be measured on day 8, with the mean arterial oxygen saturation (PaO2/FiO2) and the change in arterial oxygenation from baseline to day 8 being recorded.