Evaluation of Dexamethasone Sodium Phosphate Dosing in Acute Hypoxemic Respiratory Failure Due to Infections, Including ARDS and COVID-19

The primary objective of this study is to evaluate the effects of administering **dexamethasone** at doses of 20/10 mg versus 6 mg intravenously on the number of deaths at 60 days post-randomization and the number of days alive without ventilator support at 28 days in adult patients with **Acute Hypoxemic Respiratory Failure** (AHRF), including Acute Respiratory Distress Syndrome (ARDS), caused by pulmonary or systemic infections, such as COVID-19. This objective is clinically relevant as it aims to determine the optimal dosing strategy for dexamethasone to improve survival and reduce the need for mechanical ventilation in this patient population.

Secondary objectives include:

• Assessing the number of ventilator-free days (VFDs) at 28 days post-randomization, considering successful liberation from mechanical ventilation lasting more than 48 hours without reintubation in survivors.
• Determining the number of subjects experiencing one or more serious adverse reactions (SARs) by day 28, including new episodes of sepsis/septic shock, new pneumonia, reintubation, clinically significant gastrointestinal bleeding, or anaphylactic reaction to dexamethasone.
• Evaluating all-cause ICU mortality.
• Evaluating all-cause hospital mortality.

The clinical trial involves **adult subjects** aged 18 years and older, both male and female, who are experiencing **Acute Hypoxemic Respiratory Failure** (AHRF), including Acute Respiratory Distress Syndrome (ARDS), due to pulmonary or systemic infections such as COVID-19. Participants are required to be intubated and mechanically ventilated, with an acute onset of AHRF characterized by a PaO2/FiO2 ratio of 300 mmHg or less, maintained for at least six hours from diagnosis. The study does not include a vulnerable population. The trial population was selected based on specific inclusion criteria, including the need for ventilatory support and the presence of bilateral pulmonary infiltrates on chest imaging, without signs of left heart failure. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.

The clinical trial is a **randomized**, open-label, multicenter, phase III study designed to evaluate the efficacy of higher versus lower doses of **dexamethasone** in subjects with **acute hypoxemic respiratory failure** caused by infections, including COVID-19. The trial aims to assess the effects of 20/10 mg versus 6 mg of intravenous dexamethasone on the number of deaths at 60 days post-randomization and the number of days alive without ventilator support at 28 days, among other outcomes. The primary endpoint is all-cause hospital mortality, while secondary endpoints include the number of ventilator-free days at Day 28, mortality at ICU and Day 28, duration on mechanical ventilation, length of hospital stay for survivors, time from treatment initiation to death, and proportions with viral RNA detection over time.

The trial is expected to run until December 31, 2024, with recruitment having started on July 6, 2021. Participants will be involved in the study for a maximum treatment period of 10 days, with the possibility of early termination if they experience adverse effects or if the study is discontinued for any reason. The study includes several visits: an initial screening visit to confirm eligibility based on criteria such as age (≥18 years), mechanical ventilation requirement, and acute onset of AHRF, followed by regular follow-up visits to monitor health status and treatment response. The end-of-study visit will occur at the conclusion of the participant's involvement, where final assessments will be conducted to gather data on the primary and secondary endpoints.

The clinical trial involves the administration of **Dexamethasone Sodium Phosphate**, marketed as Dexametasona Kern Pharma 7.2 mg solución inyectable. This experimental medication is provided in the form of a **solution for injection**. The active substance, dexamethasone sodium phosphate, is of chemical origin. The trial evaluates the efficacy of different dosing regimens, specifically comparing higher doses of 20 mg per day to lower doses of 6 mg per day. The maximum daily dose is set at 20 mg, with a total maximum treatment period of 10 days. The medication is administered intravenously, and the frequency of administration is determined by the specific dosing schedule assigned to each participant. Compliance with the dosing regimen is monitored throughout the trial to ensure adherence to the protocol.

In addition to the experimental treatment, the study may include non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments, depending on the specific design of the trial. These treatments are used to provide a baseline for evaluating the efficacy of the experimental medication. The trial's objective is to assess the impact of dexamethasone on mortality rates at 60 days post-randomization and the number of days participants remain alive without ventilator support within 28 days. The study focuses on adult subjects with acute hypoxemic respiratory failure, including acute respiratory distress syndrome (ARDS), caused by infections such as COVID-19. The trial is conducted under authorized conditions, ensuring that all procedures adhere to regulatory standards and ethical guidelines.

The efficacy of the clinical trial will be assessed by evaluating the impact of different doses of **dexamethasone** on patients with acute hypoxemic respiratory failure (AHRF), including acute respiratory distress syndrome (ARDS), caused by infections such as COVID-19. The primary endpoint for efficacy assessment is all-cause hospital mortality. Secondary endpoints include the number of ventilator-free days at Day 28, mortality at the intensive care unit (ICU) and at Day 28, duration on mechanical ventilation, length of hospital stay for survivors, time from treatment initiation to death, and proportions with viral RNA detection over time.

The trial will compare the effects of 20/10 mg versus 6 mg of intravenous dexamethasone. The primary and secondary endpoints will be measured at specific timepoints, including 28 days and 60 days post-randomization. Data collection will involve recording deaths from any cause at 60 days, regardless of the patient's location, and obtaining clinical status information from electronic clinical records if subjects are discharged alive before Day 60. The trial is designed as a randomized, open-label, multicenter, phase III study, ensuring a comprehensive evaluation of the efficacy of higher versus lower doses of dexamethasone in the specified patient population.